Atherosclerosis plus最新文献_第4页

Characterization of selected LDLR substitutions in patients with familial hypercholesterolemia 家族性高胆固醇血症患者LDLR替代的特性分析

IF 2.1 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-11-18 DOI: 10.1016/j.athplu.2025.11.001

Monika Targońska , Anna Janaszak-Jasiecka , Magdalena Chmara , Monika Żuk , Leszek Kalinowski , Krzysztof Waleron , Jacek Jasiecki , Bartosz Wasąg

Background and aims

Familial hypercholesterolemia is a genetic disorder caused by pathogenic or likely pathogenic variants in four key genes: LDLR, APOB, PCSK9, and APOE. It leads to elevated levels of low-density lipoprotein cholesterol in the bloodstream and significantly increases the risk of coronary artery disease. This study aimed to functionally characterize LDLR variants identified in Polish FH patients. Experimental data were used to learn about variants' phenotypes and incorporate them into the ACMG/AMP variant classification framework.

Methods

The functional analysis was performed using the HEK293T-ldlrG1 cells with the expression vectors pTetRedLDLR carrying the mutated LDLR gene variants. Receptor expression was evaluated using Western blot and immunofluorescence. The low-density lipoprotein uptake and ligand binding capacity were examined with fluorescent dye-labeled LDL by confocal microscopy. A functional study was performed to analyze the variants under assessment and compare them to known benign and pathogenic control variants.

Results

The experimental study revealed an impaired activity of the c.662A > G p. (Asp221Gly), c.1775G > A p. (Gly592Glu), and c.2483delA p. (Tyr828Phefs∗101) LDLR variants, classifying them as functionally abnormal. In contrast, in vitro activity assessment of the c.91G > A p. (Glu31Lys) LDLR variant showed fully functional low-density lipoprotein binding and uptake activities. These results suggested that c.91G > A p. (Glu31Lys) is unlikely to be a disease-causing variant.

Conclusions

The results provide functional evidence for the activity of selected LDLR variants in a cellular model based on confocal techniques that meets the ACMG/AMP variant classification criteria. These findings highlight the importance of in vitro assays in evaluating the functional impact of LDLR variants and contribute valuable insights for clinical interpretation and genetic counseling.

背景和目的家族性高胆固醇血症是一种由LDLR、APOB、PCSK9和APOE四个关键基因的致病性或可能致病性变异引起的遗传性疾病。它会导致血液中低密度脂蛋白胆固醇水平升高，并显著增加冠状动脉疾病的风险。本研究旨在对波兰FH患者中发现的LDLR变异进行功能表征。利用实验数据了解变异的表型，并将其纳入ACMG/AMP变异分类框架。方法以携带LDLR突变基因变体的pTetRedLDLR表达载体HEK293T-ldlrG1细胞进行功能分析。采用Western blot和免疫荧光法检测受体表达。用荧光染料标记LDL共聚焦显微镜检测低密度脂蛋白摄取和配体结合能力。一项功能研究分析了评估中的变异，并将其与已知的良性和致病对照变异进行了比较。结果实验研究显示c.662A > G . (Asp221Gly), c.1775G > A . （Gly592Glu）和c.2483delA p. (Tyr828Phefs * 101) LDLR变体的活性受损，将其归类为功能异常。相比之下，c.91G > A p. (Glu31Lys) LDLR变体的体外活性评估显示出完全功能的低密度脂蛋白结合和摄取活性。这些结果表明c.91G > A p. （Glu31Lys）不太可能是致病变异。结论该结果为基于共聚焦技术的细胞模型中选定的LDLR变体的活性提供了功能证据，这些变体符合ACMG/AMP变体分类标准。这些发现强调了体外检测在评估LDLR变异的功能影响方面的重要性，并为临床解释和遗传咨询提供了有价值的见解。

{"title":"Characterization of selected LDLR substitutions in patients with familial hypercholesterolemia","authors":"Monika Targońska , Anna Janaszak-Jasiecka , Magdalena Chmara , Monika Żuk , Leszek Kalinowski , Krzysztof Waleron , Jacek Jasiecki , Bartosz Wasąg","doi":"10.1016/j.athplu.2025.11.001","DOIUrl":"10.1016/j.athplu.2025.11.001","url":null,"abstract":"<div><h3>Background and aims</h3><div>Familial hypercholesterolemia is a genetic disorder caused by pathogenic or likely pathogenic variants in four key genes: <em>LDLR</em>, <em>APOB</em>, <em>PCSK9,</em> and <em>APOE</em>. It leads to elevated levels of low-density lipoprotein cholesterol in the bloodstream and significantly increases the risk of coronary artery disease. This study aimed to functionally characterize <em>LDLR</em> variants identified in Polish FH patients. Experimental data were used to learn about variants' phenotypes and incorporate them into the ACMG/AMP variant classification framework.</div></div><div><h3>Methods</h3><div>The functional analysis was performed using the HEK293T-<em>ldlr</em>G1 cells with the expression vectors pTetRedLDLR carrying the mutated <em>LDLR</em> gene variants. Receptor expression was evaluated using Western blot and immunofluorescence. The low-density lipoprotein uptake and ligand binding capacity were examined with fluorescent dye-labeled LDL by confocal microscopy. A functional study was performed to analyze the variants under assessment and compare them to known benign and pathogenic control variants.</div></div><div><h3>Results</h3><div>The experimental study revealed an impaired activity of the c.662A > G p. (Asp221Gly), c.1775G > A p. (Gly592Glu), and c.2483delA p. (Tyr828Phefs∗101) <em>LDLR</em> variants, classifying them as functionally abnormal. In contrast, <em>in vitro</em> activity assessment of the c.91G > A p. (Glu31Lys) <em>LDLR</em> variant showed fully functional low-density lipoprotein binding and uptake activities. These results suggested that c.91G > A p. (Glu31Lys) is unlikely to be a disease-causing variant.</div></div><div><h3>Conclusions</h3><div>The results provide functional evidence for the activity of selected <em>LDLR</em> variants in a cellular model based on confocal techniques that meets the ACMG/AMP variant classification criteria. These findings highlight the importance of <em>in vitro</em> assays in evaluating the functional impact of <em>LDLR</em> variants and contribute valuable insights for clinical interpretation and genetic counseling.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"62 ","pages":"Pages 30-37"},"PeriodicalIF":2.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145579088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Earthworm fibrinolytic enzyme A and fibrin-derived peptide Bβ15-42 attenuate atherosclerosis via the VE-Cadherin signaling pathway 蚯蚓纤溶酶A和纤维蛋白衍生肽Bβ15-42通过VE-Cadherin信号通路减弱动脉粥样硬化

IF 2.1 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-10-30 DOI: 10.1016/j.athplu.2025.10.023

Xiaowei Yin , Yajie Zhang , Luyao Shi , Junwen Xue , Zhen Tian , Chicheng Gong , Fen Wang , Yongjun Cao

Aim

Earthworm fibrinolytic enzymes A (EFEa) is the main active component of earthworm fibrinolytic enzymes which possesses anticoagulant, fibrinolytic, and potential anti-atherosclerotic effects. However, the biological function and mechanism of action of EFEa remains unclear. This study aims to investigate the role of EFEa and the fibrin-derived peptide Bβ15-42 (Bβ15-42) in attenuating atherosclerosis by modulating endothelial adhesion and inflammation via the vascular endothelial (VE)-cadherin signaling pathway.

Methods

In this study, we established both a rabbit model of atherosclerosis and an in vitro endothelial cell model. Bβ15-42, EFEa, and rosuvastatin (ROS) were administered to evaluate their effects on atherosclerotic plaque formation and inflammatory responses. Plaque size and intimal thickening were evaluated using Oil Red O and hematoxylin-eosin (HE) staining. Fibrinogen deposition and VE-cadherin expression were analyzed via western blotting and immunohistochemistry. Furthermore, macrophage migration assays and CDH5-positive (CDH5⁺) human umbilical vein endothelial cell (HUVEC) models were utilized to investigate the effects of these compounds on inflammatory cell migration and VE-cadherin-mediated endothelial barrier function.

Results

Treatment with Bβ15-42, EFEa, and ROS significantly reduced atherosclerotic plaque formation and intimal thickening in the rabbit model of atherosclerosis (P < 0.05). Both Bβ15-42 and EFEa significantly reduced fibrinogen deposition and inflammatory cell infiltration in the aortic tissue of atherosclerotic rabbits (P < 0.05). Western blot and immunohistochemical analyses confirmed that Bβ15-42 and EFEa effectively up-regulated VE-cadherin expression (P < 0.05). In vitro, Bβ15-42 and EFEa significantly inhibited fibrin-induced macrophage transmigration across endothelial cell monolayers, reducing migration by 83.3 % and 56.1 %, respectively (P < 0.05, respectively).

Conclusion

EFEa and Bβ15-42 exert protective effects against atherosclerosis via the VE-cadherin pathway. Our findings lay the groundwork for further research into the anti-atherosclerotic mechanisms of EFEa, as well as its potential for future development and application.

蚯蚓纤溶酶A （EFEa）是蚯蚓纤溶酶的主要活性成分，具有抗凝血、纤溶和潜在的抗动脉粥样硬化作用。然而，EFEa的生物学功能和作用机制尚不清楚。本研究旨在探讨EFEa和纤维蛋白衍生肽Bβ15-42 （Bβ15-42）通过血管内皮(VE)-钙粘蛋白信号通路调节内皮粘附和炎症，从而减轻动脉粥样硬化的作用。方法建立家兔动脉粥样硬化模型和体外内皮细胞模型。给予Bβ15-42、EFEa和瑞舒伐他汀（ROS）以评估其对动脉粥样硬化斑块形成和炎症反应的影响。采用油红O和苏木精-伊红（HE）染色评估斑块大小和内膜增厚。western blotting和免疫组化分析纤维蛋白原沉积和VE-cadherin表达。此外，利用巨噬细胞迁移实验和CDH5阳性（CDH5+）人脐静脉内皮细胞（HUVEC）模型来研究这些化合物对炎症细胞迁移和ve -cadherin介导的内皮屏障功能的影响。结果Bβ15-42、EFEa和ROS治疗可显著降低动脉粥样硬化兔模型动脉粥样硬化斑块形成和内膜增厚（P < 0.05）。Bβ15-42和EFEa均能显著降低动脉粥样硬化兔主动脉组织纤维蛋白原沉积和炎症细胞浸润（P < 0.05）。Western blot和免疫组化分析证实，Bβ15-42和EFEa有效上调VE-cadherin的表达（P < 0.05）。在体外，Bβ15-42和EFEa显著抑制纤维蛋白诱导的巨噬细胞跨内皮细胞单层的迁移，分别减少83.3%和56.1%的迁移（P < 0.05）。结论efea和Bβ15-42通过VE-cadherin通路对动脉粥样硬化具有保护作用。本研究结果为EFEa抗动脉粥样硬化机制的进一步研究奠定了基础，并为其未来的开发和应用奠定了基础。

{"title":"Earthworm fibrinolytic enzyme A and fibrin-derived peptide Bβ15-42 attenuate atherosclerosis via the VE-Cadherin signaling pathway","authors":"Xiaowei Yin , Yajie Zhang , Luyao Shi , Junwen Xue , Zhen Tian , Chicheng Gong , Fen Wang , Yongjun Cao","doi":"10.1016/j.athplu.2025.10.023","DOIUrl":"10.1016/j.athplu.2025.10.023","url":null,"abstract":"<div><h3>Aim</h3><div>Earthworm fibrinolytic enzymes A (EFEa) is the main active component of earthworm fibrinolytic enzymes which possesses anticoagulant, fibrinolytic, and potential anti-atherosclerotic effects. However, the biological function and mechanism of action of EFEa remains unclear. This study aims to investigate the role of EFEa and the fibrin-derived peptide Bβ15-42 (Bβ15-42) in attenuating atherosclerosis by modulating endothelial adhesion and inflammation via the vascular endothelial (VE)-cadherin signaling pathway.</div></div><div><h3>Methods</h3><div>In this study, we established both a rabbit model of atherosclerosis and an in vitro endothelial cell model. Bβ15-42, EFEa, and rosuvastatin (ROS) were administered to evaluate their effects on atherosclerotic plaque formation and inflammatory responses. Plaque size and intimal thickening were evaluated using Oil Red O and hematoxylin-eosin (HE) staining. Fibrinogen deposition and VE-cadherin expression were analyzed via western blotting and immunohistochemistry. Furthermore, macrophage migration assays and CDH5-positive (CDH5<sup>+</sup>) human umbilical vein endothelial cell (HUVEC) models were utilized to investigate the effects of these compounds on inflammatory cell migration and VE-cadherin-mediated endothelial barrier function.</div></div><div><h3>Results</h3><div>Treatment with Bβ15-42, EFEa, and ROS significantly reduced atherosclerotic plaque formation and intimal thickening in the rabbit model of atherosclerosis (<em>P</em> < 0.05). Both Bβ15-42 and EFEa significantly reduced fibrinogen deposition and inflammatory cell infiltration in the aortic tissue of atherosclerotic rabbits (<em>P</em> < 0.05). Western blot and immunohistochemical analyses confirmed that Bβ15-42 and EFEa effectively up-regulated VE-cadherin expression (<em>P</em> < 0.05). In vitro, Bβ15-42 and EFEa significantly inhibited fibrin-induced macrophage transmigration across endothelial cell monolayers, reducing migration by 83.3 % and 56.1 %, respectively (<em>P</em> < 0.05, respectively).</div></div><div><h3>Conclusion</h3><div>EFEa and Bβ15-42 exert protective effects against atherosclerosis via the VE-cadherin pathway. Our findings lay the groundwork for further research into the anti-atherosclerotic mechanisms of EFEa, as well as its potential for future development and application.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"62 ","pages":"Pages 21-29"},"PeriodicalIF":2.1,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145474234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Midlife ICAM-1 levels may predict cardiovascular disease and cognitive decline in latelife: Insights from the HeartSCORE study 中年ICAM-1水平可能预测晚年心血管疾病和认知能力下降：来自HeartSCORE研究的见解

IF 2.1 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-10-14 DOI: 10.1016/j.athplu.2025.10.001

Khaled Abdoun , Justin Swanson , Ian Pollack , Yuefang Chang , Kevin Kip , Oscar L. Lopez , Ann Cohen , Steven Reis , Anum Saeed

Introduction

Systemic inflammation is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD) and has also been implicated in the progression of neuroinflammation. However, the relationship between inflammation and the combined risk of ASCVD and cognitive decline—particularly during the critical transition from midlife to late life—remains poorly understood. Identifying a shared inflammatory marker that signals vulnerability to both conditions may be an important tool for early intervention. In this study, we examined how baseline inflammatory markers, as well as their changes over one year, relate to long-term risk of ASCVD and cognitive outcomes.

Methods

We analyzed baseline and one-year change (1y-Δ) in an inflammatory biomarker panel [high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), intracellular Adhesion Molecule 1 (ICAM-1) and CD40 ligand (CD40L_)] in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study. Using logistic and linear Cox regression models, the association of inflammatory markers and 1y-Δ, cognitive assessment by MoCA score, coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and major adverse cardiovascular events (MACE) events were assessed longitudinally. All data were adjusted for the pooled cohort equation (PCE) risk factors and area under the receiver operating characteristic curve (AUC) were calculated for incremental risk prediction.

Results

Among 673 participants (mean age 59 ± 6.8 years; 63.9 % female; 31.6 % Black) were followed for 12 years. While both hs-CRP and IL-6 were associated with MACE events at 12 years, only ICAM-1 was linked with long-term MACE (HR 2.34 [1.02–5.37], p < 0.05) as well as lower MoCA scores (β: 0.47 [95 % CI: 0.93 to −0.02], p < 0.05). Compared to the PCE model, inflammatory biomarkers improved risk prediction indices for MACE (0.812, ΔAUC +0.056, p = 0.02) and MoCA (0.664, ΔAUC +0.04, p = 0.048). One-year biomarker changes were not significant for endpoint association.

Conclusions

In a community cohort of adults, midlife levels of three inflammatory markers (hs-CRP, IL-6, and ICAM-1) were predictive of late life ASCVD; however, only ICAM-1 was identified as a dual marker for ASCVD and cognitive impairment. The role of ICAM-1 as a prognostic marker for adverse cardiovascular and cognitive health should be explored in future studies.

系统性炎症是公认的动脉粥样硬化性心血管疾病（ASCVD）的危险因素，也与神经炎症的进展有关。然而，炎症与ASCVD和认知能力下降的综合风险之间的关系，特别是在从中年到晚年的关键过渡时期，仍然知之甚少。识别一种共同的炎症标志物，表明对这两种疾病的易感性，可能是早期干预的重要工具。在这项研究中，我们研究了基线炎症标志物及其在一年内的变化与ASCVD的长期风险和认知结果的关系。方法：我们分析了心脏策略集中风险评估（Heart SCORE）研究中炎症生物标志物面板[高敏c反应蛋白（hs-CRP）、白细胞介素-6 （IL-6）、细胞内粘附分子1 （ICAM-1）和CD40配体（CD40L_）]的基线和一年变化（1y-Δ）。采用logistic和线性Cox回归模型，纵向评估炎症标志物与1y-Δ、MoCA评分认知评估、冠状动脉钙（CAC）、颈动脉内膜-中膜厚度（CIMT）和主要心血管不良事件（MACE）事件的相关性。对所有数据进行合并队列方程（PCE）危险因素调整，并计算受试者工作特征曲线下面积（AUC），以进行增量风险预测。结果673例患者（平均年龄59±6.8岁，女性63.9%，黑人31.6%）随访12年。虽然hs-CRP和IL-6都与12年时的MACE事件相关，但只有ICAM-1与长期MACE （HR 2.34 [1.02-5.37], p < 0.05）以及较低的MoCA评分相关（β: 0.47 [95% CI: 0.93至- 0.02],p < 0.05）。与PCE模型相比，炎症生物标志物改善了MACE （0.812， ΔAUC +0.056, p = 0.02）和MoCA （0.664， ΔAUC +0.04, p = 0.048）的风险预测指标。一年的生物标志物变化与终点关联不显著。结论：在一个社区成人队列中，三种炎症标志物（hs-CRP、IL-6和ICAM-1）的中年水平可预测晚期ASCVD；然而，只有ICAM-1被确定为ASCVD和认知障碍的双重标志物。ICAM-1作为心血管和认知健康不良的预后标志物的作用应在未来的研究中进一步探讨。

{"title":"Midlife ICAM-1 levels may predict cardiovascular disease and cognitive decline in latelife: Insights from the HeartSCORE study","authors":"Khaled Abdoun , Justin Swanson , Ian Pollack , Yuefang Chang , Kevin Kip , Oscar L. Lopez , Ann Cohen , Steven Reis , Anum Saeed","doi":"10.1016/j.athplu.2025.10.001","DOIUrl":"10.1016/j.athplu.2025.10.001","url":null,"abstract":"<div><h3>Introduction</h3><div>Systemic inflammation is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD) and has also been implicated in the progression of neuroinflammation. However, the relationship between inflammation and the combined risk of ASCVD and cognitive decline—particularly during the critical transition from midlife to late life—remains poorly understood. Identifying a shared inflammatory marker that signals vulnerability to both conditions may be an important tool for early intervention. In this study, we examined how baseline inflammatory markers, as well as their changes over one year, relate to long-term risk of ASCVD and cognitive outcomes.</div></div><div><h3>Methods</h3><div>We analyzed baseline and one-year change (1y-Δ) in an inflammatory biomarker panel [high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), intracellular Adhesion Molecule 1 (ICAM-1) and CD40 ligand (CD40L_)] in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study. Using logistic and linear Cox regression models, the association of inflammatory markers and 1y-Δ, cognitive assessment by MoCA score, coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and major adverse cardiovascular events (MACE) events were assessed longitudinally. All data were adjusted for the pooled cohort equation (PCE) risk factors and area under the receiver operating characteristic curve (AUC) were calculated for incremental risk prediction.</div></div><div><h3>Results</h3><div>Among 673 participants (mean age 59 ± 6.8 years; 63.9 % female; 31.6 % Black) were followed for 12 years. While both hs-CRP and IL-6 were associated with MACE events at 12 years, only ICAM-1 was linked with long-term MACE (HR 2.34 [1.02–5.37], p < 0.05) as well as lower MoCA scores (β: 0.47 [95 % CI: 0.93 to −0.02], p < 0.05). Compared to the PCE model, inflammatory biomarkers improved risk prediction indices for MACE (0.812, ΔAUC +0.056, p = 0.02) and MoCA (0.664, ΔAUC +0.04, p = 0.048). One-year biomarker changes were not significant for endpoint association.</div></div><div><h3>Conclusions</h3><div>In a community cohort of adults, midlife levels of three inflammatory markers (hs-CRP, IL-6, and ICAM-1) were predictive of late life ASCVD; however, only ICAM-1 was identified as a dual marker for ASCVD and cognitive impairment. The role of ICAM-1 as a prognostic marker for adverse cardiovascular and cognitive health should be explored in future studies.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"62 ","pages":"Pages 15-20"},"PeriodicalIF":2.1,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inclisiran for fast-track lipid-lowering treatment early after an acute coronary syndrome: a pilot study 急性冠状动脉综合征后早期快速降脂治疗的Inclisiran：一项初步研究

IF 2.1 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-09-24 DOI: 10.1016/j.athplu.2025.09.005

Alessandro Lupi , Martino Baluci , Simone Persampieri , Iacopo Perversi , Davide Presutti , Alberto Somaschini , Giovanni Vincenzo Gaudio , Luigina Guasti , Marc Ferrini , Alberto Corsini , Roberto De Ponti

Background

Elevated low-density lipoprotein cholesterol (LDL-C) after acute coronary syndrome (ACS) significantly increases cardiovascular risk. Timely reduction of LDL-C is crucial, but it takes several weeks to achieve optimal LDL-C levels with standard therapy. Monoclonal antibodies that inhibit PCSK9 have been demonstrated in some small randomised trials to rapidly abate LDL-C levels when used early after hospital admission for ACS. Inclisiran, a PCSK9-inhibiting siRNA, has recently been introduced into clinical practice; however, no information is available about its effectiveness and safety as a fast-track lipid-lowering agent in this clinical context.

Methods

We conducted a prospective, real-world study evaluating a fast-track lipid-lowering approach starting inclisiran on top of standard therapy in 16 consecutive ACS patients admitted to our cardiac intensive care unit with a high baseline LDL-C level (147.2 ± 35.7 mg/dL). Patients started inclisiran as add-on therapy as soon as baseline LDL-C levels were available. We assessed LDL-C levels and the mean change of LDL-C at baseline, discharge, 15-day and 30-day follow-up.

Results

Inclisiran, added to standard therapy, reduced LDL-C levels to 30.3 ± 13.0 mg/dL at 30-day follow-up. The guideline-recommended LDL-C levels (≤55 mg/dL, ≥50 % reduction) were achieved in 73.3 % of patients at 15 days and in 100 % of patients at 30 days, with no adverse effects.

Conclusion

This pilot study shows promise for inclisiran as a novel therapeutic option to improve cardiovascular outcomes in patients with ACS by contributing to achieving an early and sustained reduction in LDL-C levels.

背景：急性冠脉综合征（ACS）后低密度脂蛋白胆固醇（LDL-C）升高显著增加心血管风险。及时降低LDL-C是至关重要的，但标准治疗需要数周时间才能达到最佳LDL-C水平。在一些小型随机试验中，抑制PCSK9的单克隆抗体已被证明在因ACS入院后早期使用可迅速降低LDL-C水平。Inclisiran是一种抑制pcsk9的siRNA，最近已被引入临床实践；然而，在这种临床背景下，没有关于其作为快速降脂剂的有效性和安全性的信息。方法：我们进行了一项前瞻性、现实世界的研究，评估了在标准治疗基础上开始使用inclisiran的快速降脂方法，对16例连续入住我们心脏重症监护病房的高基线LDL-C水平（147.2±35.7 mg/dL）的ACS患者进行了评估。患者一旦获得基线LDL-C水平，就开始使用inclisiran作为附加治疗。我们评估LDL-C水平以及基线、出院、15天和30天随访时LDL-C的平均变化。结果在标准治疗中加入inclisiran后，随访30天LDL-C水平降至30.3±13.0 mg/dL。73.3%的患者在15天达到指南推荐的LDL-C水平（≤55 mg/dL，降低≥50%），100%的患者在30天达到指南推荐的LDL-C水平，无不良反应。本初步研究显示，inclisiran有望作为一种新的治疗选择，通过促进实现早期和持续降低LDL-C水平，改善ACS患者的心血管预后。

{"title":"Inclisiran for fast-track lipid-lowering treatment early after an acute coronary syndrome: a pilot study","authors":"Alessandro Lupi , Martino Baluci , Simone Persampieri , Iacopo Perversi , Davide Presutti , Alberto Somaschini , Giovanni Vincenzo Gaudio , Luigina Guasti , Marc Ferrini , Alberto Corsini , Roberto De Ponti","doi":"10.1016/j.athplu.2025.09.005","DOIUrl":"10.1016/j.athplu.2025.09.005","url":null,"abstract":"<div><h3>Background</h3><div>Elevated low-density lipoprotein cholesterol (LDL-C) after acute coronary syndrome (ACS) significantly increases cardiovascular risk. Timely reduction of LDL-C is crucial, but it takes several weeks to achieve optimal LDL-C levels with standard therapy. Monoclonal antibodies that inhibit PCSK9 have been demonstrated in some small randomised trials to rapidly abate LDL-C levels when used early after hospital admission for ACS. Inclisiran, a PCSK9-inhibiting siRNA, has recently been introduced into clinical practice; however, no information is available about its effectiveness and safety as a fast-track lipid-lowering agent in this clinical context.</div></div><div><h3>Methods</h3><div>We conducted a prospective, real-world study evaluating a fast-track lipid-lowering approach starting inclisiran on top of standard therapy in 16 consecutive ACS patients admitted to our cardiac intensive care unit with a high baseline LDL-C level (147.2 ± 35.7 mg/dL). Patients started inclisiran as add-on therapy as soon as baseline LDL-C levels were available. We assessed LDL-C levels and the mean change of LDL-C at baseline, discharge, 15-day and 30-day follow-up.</div></div><div><h3>Results</h3><div>Inclisiran, added to standard therapy, reduced LDL-C levels to 30.3 ± 13.0 mg/dL at 30-day follow-up. The guideline-recommended LDL-C levels (≤55 mg/dL, ≥50 % reduction) were achieved in 73.3 % of patients at 15 days and in 100 % of patients at 30 days, with no adverse effects.</div></div><div><h3>Conclusion</h3><div>This pilot study shows promise for inclisiran as a novel therapeutic option to improve cardiovascular outcomes in patients with ACS by contributing to achieving an early and sustained reduction in LDL-C levels.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"62 ","pages":"Pages 9-14"},"PeriodicalIF":2.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Demographic and regional trends of mortality in patients with cardiovascular disease and liver cirrhosis in the United States between 1999 and 2019 1999年至2019年美国心血管疾病和肝硬化患者死亡率的人口统计学和区域趋势

IF 2.1 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-09-20 DOI: 10.1016/j.athplu.2025.09.004

Farah Yasmin , Abdul Moeed , Muhammad Ahmed Ali Fahim , Gaurav Kumar , Maryam Shaharyar , Muhammad Sohaib Asghar

Objectives

National estimates of deaths related to cardiovascular disease (CVD) and liver cirrhosis remain ambiguous. The purpose of this study was to observe the contemporary trends in CVD and liver cirrhosis-related mortality in the United States.

Methods

We evaluated the trends using the CDC WONDER database to identify adults with CVD and liver cirrhosis associated death between 1999 and 2019. Age-adjusted mortality rates (AAMRs) per 100,000 population and associated average annual percent changes (AAPCs) with 95 % confidence intervals (CIs) were assessed using Joinpoint regression.

Results

Between 1999 and 2019, a total of 374,090 deaths occurred due to CVD and liver cirrhosis. In the overall population, the AAMR increased from 7.54 (95 % CI 7.41–7.67) in 1999 to 10.55 (95 % CI 10.43–10.68) with an AAPC of 1.68 (95 % CI 1.59–1.77). The highest AAMRs were seen in males, Native Americans, and those living in West. A substantial increase in AAMRs was observed in all age groups with the highest seen in 70–84 year group. Moreover, non-metropolitan cities had a much higher increase in AAMRs compared to large metropolitan cities. The highest AAMRs were observed in California whereas the lowest in Utah.

Conclusion

There is a rising trend of CVD and liver cirrhosis-associated mortality in all groups. However, disparities continue to exist in association with gender, race, age, and geographical region. Future trials should address alleviating CVD and liver cirrhosis-related deaths in all population groups equitably.

目的：国家对心血管疾病（CVD）和肝硬化相关死亡的估计仍不明确。本研究的目的是观察美国心血管疾病和肝硬化相关死亡率的当代趋势。方法：我们使用CDC WONDER数据库评估1999年至2019年期间心血管疾病和肝硬化相关死亡的趋势。使用Joinpoint回归评估每10万人的年龄调整死亡率（AAMRs）和相关的年平均百分比变化（AAPCs）， 95%置信区间（ci）。结果1999年至2019年，共有374090人死于心血管疾病和肝硬化。在总体人群中，AAMR从1999年的7.54 （95% CI 7.41 ~ 7.67）增加到10.55 (95% CI 10.43 ~ 10.68)， AAPC为1.68 （95% CI 1.59 ~ 1.77）。男性、美洲原住民和居住在西部的人的aamr最高。在所有年龄组中均观察到AAMRs的显著增加，其中70-84岁组最高。此外，与大城市相比，非大城市的aamr增幅要高得多。aamr最高的是加利福尼亚州，最低的是犹他州。结论各年龄组CVD及肝硬化相关死亡率均有上升趋势。然而，与性别、种族、年龄和地理区域相关的差异仍然存在。未来的试验应在所有人群中公平地减轻心血管疾病和肝硬化相关死亡。

{"title":"Demographic and regional trends of mortality in patients with cardiovascular disease and liver cirrhosis in the United States between 1999 and 2019","authors":"Farah Yasmin , Abdul Moeed , Muhammad Ahmed Ali Fahim , Gaurav Kumar , Maryam Shaharyar , Muhammad Sohaib Asghar","doi":"10.1016/j.athplu.2025.09.004","DOIUrl":"10.1016/j.athplu.2025.09.004","url":null,"abstract":"<div><h3>Objectives</h3><div>National estimates of deaths related to cardiovascular disease (CVD) and liver cirrhosis remain ambiguous. The purpose of this study was to observe the contemporary trends in CVD and liver cirrhosis-related mortality in the United States.</div></div><div><h3>Methods</h3><div>We evaluated the trends using the CDC WONDER database to identify adults with CVD and liver cirrhosis associated death between 1999 and 2019. Age-adjusted mortality rates (AAMRs) per 100,000 population and associated average annual percent changes (AAPCs) with 95 % confidence intervals (CIs) were assessed using Joinpoint regression.</div></div><div><h3>Results</h3><div>Between 1999 and 2019, a total of 374,090 deaths occurred due to CVD and liver cirrhosis. In the overall population, the AAMR increased from 7.54 (95 % CI 7.41–7.67) in 1999 to 10.55 (95 % CI 10.43–10.68) with an AAPC of 1.68 (95 % CI 1.59–1.77). The highest AAMRs were seen in males, Native Americans, and those living in West. A substantial increase in AAMRs was observed in all age groups with the highest seen in 70–84 year group. Moreover, non-metropolitan cities had a much higher increase in AAMRs compared to large metropolitan cities. The highest AAMRs were observed in California whereas the lowest in Utah.</div></div><div><h3>Conclusion</h3><div>There is a rising trend of CVD and liver cirrhosis-associated mortality in all groups. However, disparities continue to exist in association with gender, race, age, and geographical region. Future trials should address alleviating CVD and liver cirrhosis-related deaths in all population groups equitably.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"62 ","pages":"Pages 1-8"},"PeriodicalIF":2.1,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of lipid-lowering medications on oxidized phospholipids in individuals with elevated LIPOPROTEIN(a) 降脂药物对脂蛋白升高个体氧化磷脂的影响(a)

IF 2.1 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-09-01 DOI: 10.1016/j.athplu.2025.09.003

Amalia Despoina Koutsogianni , Fotios Barkas , Constantinos Tellis , Alexandros Tselepis , George Liamis , Sotirios Tsimikas , Evangelos Liberopoulos

Background/introduction

Oxidized phospholipids (OxPLs) are bound to apolipoprotein B-100 (OxPL-apoB) and apolipoprotein(a) [OxPL-apo(a)] and are present freely within the phospholipid shell of apoB-containing lipoproteins. OxPLs have been linked with the pro-inflammatory properties of lipoprotein(a) [Lp(a)]. OxPLs carried on plasminogen (OxPL-PLG) may extend the time to fibrinolysis.

Purpose

To evaluate the effect of lipid-lowering medications on OxPLs levels in individuals with elevated Lp(a) concentrations.

Methods

In this prospective study, patients (n = 70) with Lp(a) levels ≥75 nmol/L were assigned to 3 treatment regimens according to current guidelines: high-intensity statin monotherapy (n = 28), ezetimibe added to high-intensity statin (n = 31) and proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) added to high-intensity statin plus ezetimibe (n = 11). Follow-up duration was 3 months.

Results

Patients had a mean age of 51 ± 15 years, 40 % were male, 39 % were diagnosed with familial hypercholesterolemia, 16 % had atherosclerotic cardiovascular disease, and 36 %, 33 % and 15 % were at very high, high, and moderate cardiovascular risk, respectively. Lp(a) levels did not change significantly with high-intensity statin and add-on ezetimibe but significantly decreased with add-on PCSK9i treatment. OxPL-apoB and OxPL-apo(a) significantly increased, while OxPL-PLG significantly decreased with both high-intensity statin and add-on ezetimibe. Add-on PCSK9i treatment was associated with no significant changes in OxPL-apoB, OxPL-apo(a) and OxPL-PLG levels.

Conclusions

Among patients with elevated Lp(a), both high-intensity statin and add-on ezetimibe significantly increased OxPL-apoB and OxPL-apo(a) levels, while significantly decreased OxPL-PLG levels. Add-on PCSK9i had no significant effect on OxPLs levels. The clinical implications of these findings should be further explored.

氧化磷脂（OxPLs）与载脂蛋白B-100 （OxPL-apoB）和载脂蛋白(a) [OxPL-apo(a)]结合，并自由存在于含载脂蛋白的磷脂壳内。OxPLs与脂蛋白的促炎特性有关(a) [Lp(a)]。携带纤溶酶原（OxPL-PLG）的oxpl可延长纤溶时间。目的探讨降脂药物对Lp(a)浓度升高患者OxPLs水平的影响。方法在本前瞻性研究中，Lp(a)水平≥75 nmol/L的患者（n = 70）根据现行指南分为3个治疗方案：高强度他汀单药治疗（n = 28），在高强度他汀基础上加依泽替米贝（n = 31），在高强度他汀+依泽替米贝基础上加蛋白转化酶subtilisin/ keexin 9型抑制剂（PCSK9i）治疗（n = 11）。随访时间3个月。结果患者平均年龄为51±15岁，40%为男性，39%诊断为家族性高胆固醇血症，16%患有动脉粥样硬化性心血管疾病，36%、33%和15%分别为心血管高危、高危和中度风险。Lp(a)水平在高强度他汀类药物和加用依折替布治疗组无显著变化，但在加用PCSK9i治疗组显著降低。高强度他汀类药物和附加依可替米贝组OxPL-apoB和OxPL-apo(a)均显著升高，OxPL-PLG均显著降低。附加PCSK9i治疗与OxPL-apoB、OxPL-apo(a)和OxPL-PLG水平无显著变化相关。结论在Lp(a)升高的患者中，高强度他汀和加药依泽替米贝均可显著提高OxPL-apoB和OxPL-apo(a)水平，同时显著降低OxPL-PLG水平。添加PCSK9i对OxPLs水平无显著影响。这些发现的临床意义有待进一步探讨。

{"title":"Effect of lipid-lowering medications on oxidized phospholipids in individuals with elevated LIPOPROTEIN(a)","authors":"Amalia Despoina Koutsogianni , Fotios Barkas , Constantinos Tellis , Alexandros Tselepis , George Liamis , Sotirios Tsimikas , Evangelos Liberopoulos","doi":"10.1016/j.athplu.2025.09.003","DOIUrl":"10.1016/j.athplu.2025.09.003","url":null,"abstract":"<div><h3>Background/introduction</h3><div>Oxidized phospholipids (OxPLs) are bound to apolipoprotein B-100 (OxPL-apoB) and apolipoprotein(a) [OxPL-apo(a)] and are present freely within the phospholipid shell of apoB-containing lipoproteins. OxPLs have been linked with the pro-inflammatory properties of lipoprotein(a) [Lp(a)]. OxPLs carried on plasminogen (OxPL-PLG) may extend the time to fibrinolysis.</div></div><div><h3>Purpose</h3><div>To evaluate the effect of lipid-lowering medications on OxPLs levels in individuals with elevated Lp(a) concentrations.</div></div><div><h3>Methods</h3><div>In this prospective study, patients (n = 70) with Lp(a) levels ≥75 nmol/L were assigned to 3 treatment regimens according to current guidelines: high-intensity statin monotherapy (n = 28), ezetimibe added to high-intensity statin (n = 31) and proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) added to high-intensity statin plus ezetimibe (n = 11). Follow-up duration was 3 months.</div></div><div><h3>Results</h3><div>Patients had a mean age of 51 ± 15 years, 40 % were male, 39 % were diagnosed with familial hypercholesterolemia, 16 % had atherosclerotic cardiovascular disease, and 36 %, 33 % and 15 % were at very high, high, and moderate cardiovascular risk, respectively. Lp(a) levels did not change significantly with high-intensity statin and add-on ezetimibe but significantly decreased with add-on PCSK9i treatment. OxPL-apoB and OxPL-apo(a) significantly increased, while OxPL-PLG significantly decreased with both high-intensity statin and add-on ezetimibe. Add-on PCSK9i treatment was associated with no significant changes in OxPL-apoB, OxPL-apo(a) and OxPL-PLG levels.</div></div><div><h3>Conclusions</h3><div>Among patients with elevated Lp(a), both high-intensity statin and add-on ezetimibe significantly increased OxPL-apoB and OxPL-apo(a) levels, while significantly decreased OxPL-PLG levels. Add-on PCSK9i had no significant effect on OxPLs levels. The clinical implications of these findings should be further explored.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"61 ","pages":"Pages 58-66"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inclisiran in a real-world single-center registry of patients with very high atherosclerotic cardiovascular risk 在一个真实世界的单中心注册的患者非常高的动脉粥样硬化性心血管风险

IF 2.1 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-09-01 DOI: 10.1016/j.athplu.2025.09.001

Antonio Centola , Michelangelo Carbonara , Serena De Nuzzo , Andrea Cuculo , Antonio Ruggiero , Giulio Campanale , Massimo Iacoviello , Paola Gargiulo , Pasquale Perrone Filardi , Natale Daniele Brunetti

Background

A mean relative 50 % reduction of LDL cholesterol (LDLc) levels was observed in randomized studies in patients treated with inclisiran, a small-interfering-RNA therapeutic agent that reduces hepatic synthesis of PCSK9. Less is known on real world and every-day practice patients.

Methods

Fifty consecutive patients with or at risk of atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH) and treated with inclisiran according to Italian indications were enrolled in an observational study. LDLc levels were followed up.

Results

26 patients had an acute coronary syndrome (ACS), 11 FH; 46 % were on high-intensity statin therapy, 68 % on combination therapy statin/ezetimibe.

Mean LDLc level of the study population was 118 ± 12 mg/dl at baseline, 80 ± 18 mg/dl after 3 months, and 70 ± 15 mg/dl after 6 months (ANOVA p < 0.001). The use of inclisiran was associated with significantly reduced LDLc levels of 21 % at 1 month and 44 % at 6 months.

LDLc reduction in patients with ACS was statistically significant and comparable with chronic CS. Patients receiving a background combination therapy (statin/ezetimibe) showed a greater reduction in circulating LDLc levels than patients using inclisiran alone. No significant side effects or treatment drop out were observed during follow up. Rates of subjects with LDLc levels below 70 mg/dl (Italian Drug Agency target) increased from 0 % at baseline to 56 % at 6 months (p < 0.001).

Conclusions

In a real-world population 3–6 months of therapy with inclisiran provide consistent and effective reduction in LDLc levels without significant adverse side-effects.

在随机研究中，接受inclisiran治疗的患者LDL胆固醇（LDLc）水平平均相对降低50%。inclisiran是一种小干扰rna治疗药物，可减少肝脏PCSK9的合成。对现实世界和日常实践患者的了解较少。方法：连续50例动脉粥样硬化性心血管疾病（ASCVD）或家族性高胆固醇血症（FH）患者，并根据意大利适应症接受inclisiran治疗，纳入观察性研究。跟踪ldl水平。结果急性冠脉综合征（ACS） 26例，FH 11例；46%接受高强度他汀类药物治疗，68%接受他汀/依折麦布联合治疗。研究人群的平均ldl水平基线时为118±12 mg/dl， 3个月后为80±18 mg/dl， 6个月后为70±15 mg/dl（方差分析p <； 0.001）。使用inclisiran可显著降低ldl水平，1个月时降低21%，6个月时降低44%。ACS患者ldl降低具有统计学意义，与慢性CS相当。接受背景联合治疗（他汀/依折麦布）的患者比单独使用inclisiran的患者循环ldl水平下降更大。随访期间未观察到明显的副作用或治疗退出。ldl水平低于70 mg/dl（意大利药品管理局目标）的受试者比率从基线时的0%增加到6个月时的56% （p < 0.001）。结论：在现实世界人群中，使用inclisiran治疗3-6个月可以持续有效地降低ldl水平，且没有明显的不良副作用。

{"title":"Inclisiran in a real-world single-center registry of patients with very high atherosclerotic cardiovascular risk","authors":"Antonio Centola , Michelangelo Carbonara , Serena De Nuzzo , Andrea Cuculo , Antonio Ruggiero , Giulio Campanale , Massimo Iacoviello , Paola Gargiulo , Pasquale Perrone Filardi , Natale Daniele Brunetti","doi":"10.1016/j.athplu.2025.09.001","DOIUrl":"10.1016/j.athplu.2025.09.001","url":null,"abstract":"<div><h3>Background</h3><div>A mean relative 50 % reduction of LDL cholesterol (LDLc) levels was observed in randomized studies in patients treated with inclisiran, a small-interfering-RNA therapeutic agent that reduces hepatic synthesis of PCSK9. Less is known on real world and every-day practice patients.</div></div><div><h3>Methods</h3><div>Fifty consecutive patients with or at risk of atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH) and treated with inclisiran according to Italian indications were enrolled in an observational study. LDLc levels were followed up.</div></div><div><h3>Results</h3><div>26 patients had an acute coronary syndrome (ACS), 11 FH; 46 % were on high-intensity statin therapy, 68 % on combination therapy statin/ezetimibe.</div><div>Mean LDLc level of the study population was 118 ± 12 mg/dl at baseline, 80 ± 18 mg/dl after 3 months, and 70 ± 15 mg/dl after 6 months (ANOVA p < 0.001). The use of inclisiran was associated with significantly reduced LDLc levels of 21 % at 1 month and 44 % at 6 months.</div><div>LDLc reduction in patients with ACS was statistically significant and comparable with chronic CS. Patients receiving a background combination therapy (statin/ezetimibe) showed a greater reduction in circulating LDLc levels than patients using inclisiran alone. No significant side effects or treatment drop out were observed during follow up. Rates of subjects with LDLc levels below 70 mg/dl (Italian Drug Agency target) increased from 0 % at baseline to 56 % at 6 months (p < 0.001).</div></div><div><h3>Conclusions</h3><div>In a real-world population 3–6 months of therapy with inclisiran provide consistent and effective reduction in LDLc levels without significant adverse side-effects.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"61 ","pages":"Pages 67-72"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Monocytes from people with Familial Hypercholesterolaemia are inflammatory, despite statin-treatment 尽管他汀类药物治疗，家族性高胆固醇血症患者的单核细胞仍具有炎症性

IF 2.1 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-09-01 DOI: 10.1016/j.athplu.2025.09.002

Helen Williams , Habib Francis , Jasmin Huang , Rekha Marimuthu , Rana Baraz , Heather Medbury , Stephen Li

Background and aims

Familial Hypercholesterolaemia (FH) is characterised by high cholesterol and premature cardiovascular disease. While hypercholesterolaemia and inflammation are both key drivers in the formation of atherosclerotic plaques, inflammation remains understudied in FH. Inflammatory (M1) macrophages contribute to plaque destabilisation and macrophage precursors, monocytes, can be skewed towards an inflammatory state. Aims: Determine; whether monocytes of FH individuals are inflammatory, if they readily form inflammatory macrophages, and whether this remains so in statin-treated individuals.

Methods

Blood samples were collected from people with FH (statin-treated and untreated) and healthy controls. Lipid profile was obtained and monocyte inflammatory marker expression was determined by whole blood flow cytometry. Monocytes were cultured with autologous serum and resultant macrophage profile determined by flow cytometry.

Results

Total cholesterol and low-density lipoprotein cholesterol (LDL-C) were higher in the Untreated-FH group compared to the Treated-FH group and controls. In both Treated-FH and Untreated-FH groups, monocytes were inflammatory with high CD86 (M1). The ratio of inflammatory/anti-inflammatory markers (CD86/CD163) significantly correlated with LDL-C and ApoB/ApoA1 ratio across the cohort, indicating the high LDL-C of FH may promote an inflammatory monocyte profile. Monocyte-derived-macrophages from (Treated) FH individuals also had a more inflammatory profile (CD86 and CD86/CD163).

Conclusions

Overall, monocytes show inflammatory skewing in FH individuals, even those with moderately-reduced cholesterol levels. These monocytes readily become inflammatory macrophages. This, along with subsequent inflammatory macrophage formation, could contribute to plaque destabilisation and downstream clinical events. This supports inflammatory monocyte targeting as a potential approach to reduce residual risk in FH individuals.

背景和目的家族性高胆固醇血症（FH）以高胆固醇和早发心血管疾病为特征。虽然高胆固醇血症和炎症都是动脉粥样硬化斑块形成的关键驱动因素，但炎症在FH中的研究仍然不足。炎性（M1）巨噬细胞有助于斑块不稳定和巨噬细胞前体，单核细胞，可以偏向炎症状态。目的:确定;FH个体的单核细胞是否具有炎性，它们是否容易形成炎性巨噬细胞，以及在他汀类药物治疗的个体中是否仍然如此。方法采集FH患者（他汀治疗组和未治疗组）和健康对照者的血液样本。通过全血流式细胞术检测脂质谱和单核细胞炎症标志物的表达。用自体血清培养单核细胞，用流式细胞术测定巨噬细胞谱。结果fh治疗组总胆固醇和低密度脂蛋白胆固醇（LDL-C）高于fh治疗组和对照组。fh治疗组和未治疗组单核细胞均呈炎性，CD86 （M1）升高。在整个队列中，炎症/抗炎标志物（CD86/CD163）的比值与LDL-C和ApoB/ApoA1比值显著相关，表明FH的高LDL-C可能促进炎症单核细胞谱。来自（治疗）FH个体的单核细胞衍生巨噬细胞也具有更多的炎症谱（CD86和CD86/CD163）。总体而言，FH个体的单核细胞表现出炎症偏态，即使是胆固醇水平适度降低的个体。这些单核细胞很容易变成炎性巨噬细胞。这与随后的炎性巨噬细胞形成一起，可能导致斑块不稳定和下游临床事件。这支持炎症单核细胞靶向作为减少FH个体残留风险的潜在方法。

{"title":"Monocytes from people with Familial Hypercholesterolaemia are inflammatory, despite statin-treatment","authors":"Helen Williams , Habib Francis , Jasmin Huang , Rekha Marimuthu , Rana Baraz , Heather Medbury , Stephen Li","doi":"10.1016/j.athplu.2025.09.002","DOIUrl":"10.1016/j.athplu.2025.09.002","url":null,"abstract":"<div><h3>Background and aims</h3><div>Familial Hypercholesterolaemia (FH) is characterised by high cholesterol and premature cardiovascular disease. While hypercholesterolaemia and inflammation are both key drivers in the formation of atherosclerotic plaques, inflammation remains understudied in FH. Inflammatory (M1) macrophages contribute to plaque destabilisation and macrophage precursors, monocytes, can be skewed towards an inflammatory state. Aims: Determine; whether monocytes of FH individuals are inflammatory, if they readily form inflammatory macrophages, and whether this remains so in statin-treated individuals.</div></div><div><h3>Methods</h3><div>Blood samples were collected from people with FH (statin-treated and untreated) and healthy controls. Lipid profile was obtained and monocyte inflammatory marker expression was determined by whole blood flow cytometry. Monocytes were cultured with autologous serum and resultant macrophage profile determined by flow cytometry.</div></div><div><h3>Results</h3><div>Total cholesterol and low-density lipoprotein cholesterol (LDL-C) were higher in the Untreated-FH group compared to the Treated-FH group and controls. In both Treated-FH and Untreated-FH groups, monocytes were inflammatory with high CD86 (M1). The ratio of inflammatory/anti-inflammatory markers (CD86/CD163) significantly correlated with LDL-C and ApoB/ApoA1 ratio across the cohort, indicating the high LDL-C of FH may promote an inflammatory monocyte profile. Monocyte-derived-macrophages from (Treated) FH individuals also had a more inflammatory profile (CD86 and CD86/CD163).</div></div><div><h3>Conclusions</h3><div>Overall, monocytes show inflammatory skewing in FH individuals, even those with moderately-reduced cholesterol levels. These monocytes readily become inflammatory macrophages. This, along with subsequent inflammatory macrophage formation, could contribute to plaque destabilisation and downstream clinical events. This supports inflammatory monocyte targeting as a potential approach to reduce residual risk in FH individuals.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"61 ","pages":"Pages 73-81"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The association between dolutegravir based first-line antiretroviral regimens and dyslipidemia among adults living with HIV on follow-up at health facilities in Hawassa city administration, Sidama region: a cross-sectional study 在西达马地区哈瓦萨市政府卫生机构随访中，以多替格拉韦为基础的一线抗逆转录病毒治疗方案与成年艾滋病毒感染者血脂异常之间的关系：一项横断面研究

IF 2.1 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-08-06 DOI: 10.1016/j.athplu.2025.08.001

Agete Tadewos Hirigo , Alemayehu Abera , Daniel Yilma , Ayalew Astatkie , Zelalem Debebe

Background

Inconsistent evidence on lipid alterations in people living with HIV (PLWH) on dolutegravir (DTG)-based antiretroviral therapy (ART) highlights the need for further study. This study aimed to assess the association between DTG-based regimens and dyslipidemia among adults initiated on ART after the test-and-treat implementation in Ethiopia.

Methods

A cross-sectional study was conducted in Hawassa City Administration, Sidama region, southern Ethiopia from January 2023 to May 2024. Participants were selected using systematic random sampling. Sociodemographic, clinical, and other relevant data were collected using a semi-structured questionnaire, supplemented by a review of medical records. Dyslipidaemia was classified based on the NCEP ATP III guidelines. A binary logistic regression model was fitted to identify factors associated with dyslipidemia. An adjusted odds ratio (aORs) and 95 % confidence intervals (CIs) were computed to determine the strength of the association, with statistical significance set at p < 0.05.

Results

Of the 465 eligible adults, 450 participated in the study, attaining a response rate of 96.8 %. Of these, 262 (58.2 %) were female. Overall, 74.0 % (95 % CI: 69.8 %–78.0 %) of participants had dyslipidemia, with a higher prevalence in males (79.8 %) than in females (69.8 %). Low HDL-cholesterol was the most common lipid abnormality (66.4%), followed by high triglyceride and elevated total cholesterol/HDL-cholesterol ratio (each 34.2 %). ART initiation with DTG-based first-line regimen (aOR: 4.8; 95 %CI: 1.2–18.5), increased waist circumference (aOR: 1.06; 95 %CI: 1.01–1.11) and neck circumference (aOR: 1.2; 95 %CI: 1.06–1.5) were significantly associated with dyslipidemia.

Conclusion

Based on the study findings, we recommend that routine lipid monitoring be integrated into the clinical management of PLWH on ART, to enable early detection and timely intervention for dyslipidemia.

背景：在多替格拉韦（DTG）为基础的抗逆转录病毒治疗（ART）中，HIV感染者（PLWH）的脂质改变的一致证据强调了进一步研究的必要性。本研究旨在评估在埃塞俄比亚实施测试和治疗后开始接受抗逆转录病毒治疗的成人中以dtg为基础的方案与血脂异常之间的关系。方法于2023年1月至2024年5月在埃塞俄比亚南部Sidama地区的Hawassa市政府进行横断面研究。研究对象采用系统随机抽样的方法进行选择。使用半结构化问卷收集社会人口统计、临床和其他相关数据，并辅以对医疗记录的回顾。根据NCEP ATP III指南对血脂异常进行分类。采用二元logistic回归模型确定与血脂异常相关的因素。计算调整的优势比（aORs）和95%置信区间（ci）来确定相关性的强度，统计学显著性设置为p <；0.05.结果在465名符合条件的成年人中，有450人参与了研究，反应率为96.8%。其中女性262人（58.2%）。总体而言，74.0% （95% CI: 69.8% - 78.0%）的参与者患有血脂异常，男性患病率（79.8%）高于女性（69.8%）。低hdl -胆固醇是最常见的脂质异常（66.4%），其次是高甘油三酯和总胆固醇/ hdl -胆固醇比值升高（各为34.2%）。以dtg为基础的一线方案开始ART治疗(aOR: 4.8；95% CI: 1.2-18.5)，腰围增加(aOR: 1.06；95% CI: 1.01-1.11)和颈围(aOR: 1.2；95% CI: 1.06-1.5)与血脂异常显著相关。结论基于本研究结果，我们建议将常规血脂监测纳入抗逆转录病毒治疗PLWH的临床管理中，以实现对血脂异常的早期发现和及时干预。

{"title":"The association between dolutegravir based first-line antiretroviral regimens and dyslipidemia among adults living with HIV on follow-up at health facilities in Hawassa city administration, Sidama region: a cross-sectional study","authors":"Agete Tadewos Hirigo , Alemayehu Abera , Daniel Yilma , Ayalew Astatkie , Zelalem Debebe","doi":"10.1016/j.athplu.2025.08.001","DOIUrl":"10.1016/j.athplu.2025.08.001","url":null,"abstract":"<div><h3>Background</h3><div>Inconsistent evidence on lipid alterations in people living with HIV (PLWH) on dolutegravir (DTG)-based antiretroviral therapy (ART) highlights the need for further study. This study aimed to assess the association between DTG-based regimens and dyslipidemia among adults initiated on ART after the test-and-treat implementation in Ethiopia.</div></div><div><h3>Methods</h3><div>A cross-sectional study was conducted in Hawassa City Administration, Sidama region, southern Ethiopia from January 2023 to May 2024. Participants were selected using systematic random sampling. Sociodemographic, clinical, and other relevant data were collected using a semi-structured questionnaire, supplemented by a review of medical records. Dyslipidaemia was classified based on the NCEP ATP III guidelines. A binary logistic regression model was fitted to identify factors associated with dyslipidemia. An adjusted odds ratio (aORs) and 95 % confidence intervals (CIs) were computed to determine the strength of the association, with statistical significance set at p < 0.05.</div></div><div><h3>Results</h3><div>Of the 465 eligible adults, 450 participated in the study, attaining a response rate of 96.8 %. Of these, 262 (58.2 %) were female. Overall, 74.0 % (95 % CI: 69.8 %–78.0 %) of participants had dyslipidemia, with a higher prevalence in males (79.8 %) than in females (69.8 %). Low HDL-cholesterol was the most common lipid abnormality (66.4%), followed by high triglyceride and elevated total cholesterol/HDL-cholesterol ratio (each 34.2 %). ART initiation with DTG-based first-line regimen (aOR: 4.8; 95 %CI: 1.2–18.5), increased waist circumference (aOR: 1.06; 95 %CI: 1.01–1.11) and neck circumference (aOR: 1.2; 95 %CI: 1.06–1.5) were significantly associated with dyslipidemia.</div></div><div><h3>Conclusion</h3><div>Based on the study findings, we recommend that routine lipid monitoring be integrated into the clinical management of PLWH on ART, to enable early detection and timely intervention for dyslipidemia.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"61 ","pages":"Pages 48-57"},"PeriodicalIF":2.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144828726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging cytokines contribute to the clinical manifestation of carotid artery plaque formation and stability in patients with diabetes 新出现的细胞因子有助于糖尿病患者颈动脉斑块形成和稳定的临床表现

IF 2.1 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-08-05 DOI: 10.1016/j.athplu.2025.07.003

Zhongqing Xu , James Healy , Wenhui Dong , JingJing Ding , Xiaoyi Shen , Xianzhen Feng , Jun Zhou , Rajesh Puranik , Brett D. Hambly , Shisan Bao

Background

Type 2 diabetes mellitus (T2DM) promotes atherosclerosis and plaque instability through chronic inflammation and immune dysregulation. Emerging evidence implicates members of the interleukin-1 family—particularly IL-36, IL-37, and IL-38—in the modulation of inflammatory responses in diabetic and non-diabetic vascular disease. However, their roles in carotid atherosclerosis remain poorly defined.

Methods

In this retrospective observational study, circulating cytokine levels were assessed in 20 T2DM and 40 non-DM individuals using ELISA. Carotid plaque samples (n = 50) were collected from endarterectomy procedures and categorised as stable (asymptomatic, n = 25) or unstable (symptomatic, n = 25) according to AHA criteria. Immunohistochemistry quantified local expression of IL-36α, IL-36β, IL-36γ, IL-37, and IL-38.

Results

Circulating IL-36α, IL-36β and IL-36γ were significantly elevated in T2DM patients, while IL-37 and IL-38 levels were unchanged. Immunohistochemistry revealed significantly increased expression of all five cytokines in unstable versus stable plaques. Stratification by diabetic status showed that this upregulation was exclusive to diabetic patients. Notably, IL-36β exhibited the most pronounced increase—over 25-fold—in unstable diabetic plaques. IL-37 and IL-38 were also elevated locally, likely reflecting compensatory anti-inflammatory responses, though their circulating levels remained unaffected.

Conclusions

This study demonstrates differential expression of IL-36, IL-37, and IL-38 in carotid atherosclerotic plaques, with IL-36β emerging as a key pro-atherogenic cytokine in the diabetic setting. The distinct expression patterns of these cytokines in diabetic versus non-diabetic plaques suggest that T2DM exacerbates immune imbalance in atherosclerosis. These findings may inform future research on cytokine-targeted therapies for diabetic vascular complications.

背景2型糖尿病（T2DM）通过慢性炎症和免疫失调促进动脉粥样硬化和斑块不稳定。新出现的证据表明，白细胞介素-1家族的成员，特别是IL-36、IL-37和il -38，参与了糖尿病和非糖尿病血管疾病炎症反应的调节。然而，它们在颈动脉粥样硬化中的作用仍不明确。方法采用ELISA法对20例2型糖尿病患者和40例非糖尿病患者的循环细胞因子水平进行回顾性观察。从动脉内膜切除术中收集颈动脉斑块样本（n = 50），并根据AHA标准将其分为稳定（无症状，n = 25）或不稳定（有症状，n = 25）。免疫组织化学定量IL-36α、IL-36β、IL-36γ、IL-37和IL-38的局部表达。结果T2DM患者外周血IL-36α、IL-36β、IL-36γ水平明显升高，IL-37、IL-38水平无明显变化。免疫组织化学显示，在不稳定斑块和稳定斑块中，所有五种细胞因子的表达显著增加。按糖尿病状态分层显示，这种上调是糖尿病患者独有的。值得注意的是，IL-36β在不稳定的糖尿病斑块中表现出最明显的增加，超过25倍。IL-37和IL-38也在局部升高，可能反映了代偿性抗炎反应，尽管它们的循环水平未受影响。结论：IL-36、IL-37和IL-38在颈动脉粥样硬化斑块中的表达存在差异，IL-36β在糖尿病患者中是促动脉粥样硬化的关键细胞因子。这些细胞因子在糖尿病斑块和非糖尿病斑块中的不同表达模式表明，T2DM加重了动脉粥样硬化中的免疫失衡。这些发现可能为未来的细胞因子靶向治疗糖尿病血管并发症的研究提供信息。

{"title":"Emerging cytokines contribute to the clinical manifestation of carotid artery plaque formation and stability in patients with diabetes","authors":"Zhongqing Xu , James Healy , Wenhui Dong , JingJing Ding , Xiaoyi Shen , Xianzhen Feng , Jun Zhou , Rajesh Puranik , Brett D. Hambly , Shisan Bao","doi":"10.1016/j.athplu.2025.07.003","DOIUrl":"10.1016/j.athplu.2025.07.003","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 diabetes mellitus (T2DM) promotes atherosclerosis and plaque instability through chronic inflammation and immune dysregulation. Emerging evidence implicates members of the interleukin-1 family—particularly IL-36, IL-37, and IL-38—in the modulation of inflammatory responses in diabetic and non-diabetic vascular disease. However, their roles in carotid atherosclerosis remain poorly defined.</div></div><div><h3>Methods</h3><div>In this retrospective observational study, circulating cytokine levels were assessed in 20 T2DM and 40 non-DM individuals using ELISA. Carotid plaque samples (n = 50) were collected from endarterectomy procedures and categorised as stable (asymptomatic, n = 25) or unstable (symptomatic, n = 25) according to AHA criteria. Immunohistochemistry quantified local expression of IL-36α, IL-36β, IL-36γ, IL-37, and IL-38.</div></div><div><h3>Results</h3><div>Circulating IL-36α, IL-36β and IL-36γ were significantly elevated in T2DM patients, while IL-37 and IL-38 levels were unchanged. Immunohistochemistry revealed significantly increased expression of all five cytokines in unstable versus stable plaques. Stratification by diabetic status showed that this upregulation was exclusive to diabetic patients. Notably, IL-36β exhibited the most pronounced increase—over 25-fold—in unstable diabetic plaques. IL-37 and IL-38 were also elevated locally, likely reflecting compensatory anti-inflammatory responses, though their circulating levels remained unaffected.</div></div><div><h3>Conclusions</h3><div>This study demonstrates differential expression of IL-36, IL-37, and IL-38 in carotid atherosclerotic plaques, with IL-36β emerging as a key pro-atherogenic cytokine in the diabetic setting. The distinct expression patterns of these cytokines in diabetic versus non-diabetic plaques suggest that T2DM exacerbates immune imbalance in atherosclerosis. These findings may inform future research on cytokine-targeted therapies for diabetic vascular complications.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"61 ","pages":"Pages 41-47"},"PeriodicalIF":2.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0