Atherosclerosis plus最新文献_第6页

ApoE [−/−] CA1-overexpressing knock-in mice aggravated atherosclerosis by increasing M1 macrophages ApoE[−/−]ca1过表达敲入小鼠通过增加M1巨噬细胞加重动脉粥样硬化

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-03-27 DOI: 10.1016/j.athplu.2025.03.003

Jinbao Zong , Changyuan Wang , Hongji Zhou , Yu Song , Kehua Fang , Xiaotian Chang

Background

Carbonic anhydrase I (CA1) has been reported to be a diagnostic and therapeutic target for atherosclerosis (AS). This study aimed to verify the essential role of CA1 in AS progression in CA1-overexpressing mice.

Methods

A ApoE [−/−] CA1-overexpressing knock-in mouse model was constructed via CRISPR/Cas9-mediated genome engineering. AS was then induced in these transgenic mice via the administration of a high-fat diet, and a second group simultaneously received treatment with methazolamide (MTZ), a carbonic anhydrase inhibitor.

Results

Compared with ApoE [−/−] mice without CA1 overexpression, CA1-overexpressing mice had a greater average body weight, regardless of whether their treatment with MTZ or their AS induction status. Sudan IV, hematoxylin and eosin and Oil Red O staining revealed more plaques and fat deposits in the cardiac aortas of CA1-overexpressing mice than in those of ordinary ApoE−/− mice when AS was induced. Moreover, the atherogenic index; low-density lipoprotein, total cholesterol and triglyceride levels were significantly elevated, and high-density lipoprotein levels were declined in the peripheral blood of CA1-overexpressing mice than in that of ordinary ApoE [−/−] mice, regardless of whether these animals were induced to AS. Immunohistochemistry, Von Kossa staining and fluorescence immunohistochemistry revealed increases in CA1 expression, calcium deposition and M1 macrophages in the aortic tissues of CA1-overexpressing mice with AS. MTZ treatment significantly suppressed AS pathologies in the above experiments.

Conclusion

These findings revealed aggravated AS in ApoE [−/−] CA1-overexpressing mice and suggest that CA1 aggravates AS by increasing M1-type macrophages, a proinflammatory macrophage subtype.

碳酸酐酶I （CA1）已被报道为动脉粥样硬化（AS）的诊断和治疗靶点。本研究旨在验证CA1在CA1过表达小鼠AS进展中的重要作用。方法采用CRISPR/ cas9介导的基因组工程技术，构建过表达ApoE[−/−]ca1的敲入小鼠模型。然后通过高脂肪饮食在这些转基因小鼠中诱导AS，第二组同时接受甲基唑胺（MTZ）治疗，一种碳酸酐酶抑制剂。结果与没有CA1过表达的ApoE[−/−]小鼠相比，CA1过表达小鼠的平均体重更大，无论是MTZ治疗还是AS诱导状态。苏丹红、苏木精、伊红和油红O染色显示，AS诱导时，ca1过表达小鼠的心主动脉斑块和脂肪沉积比普通ApoE−/−小鼠多。此外，动脉粥样硬化指数；ca1过表达小鼠的外周血低密度脂蛋白、总胆固醇和甘油三酯水平显著升高，高密度脂蛋白水平低于普通ApoE[−/−]小鼠，无论这些动物是否被诱导为AS。免疫组织化学、Von Kossa染色和荧光免疫组织化学显示，过表达CA1的AS小鼠主动脉组织中CA1表达、钙沉积和M1巨噬细胞增加。在上述实验中，MTZ治疗明显抑制AS病理。结论ApoE[−/−]CA1过表达小鼠的AS加重，提示CA1通过增加促炎巨噬细胞亚型m1型加重AS。

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引用次数: 0

Real-world management of hypercholesterolemia in patients after acute coronary syndrome in Greece 希腊急性冠状动脉综合征患者高胆固醇血症的现实世界管理

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-03-24 DOI: 10.1016/j.athplu.2025.03.002

Despoina Massia , Periklis Giovas , Nikolaos Papadopoulos , Georgios Katsimagklis , Evangelos Pissimisis , Sotirios Patsilinakos , Evgenia Pappa , Giannis Baltogiannis , Nikolaos Kouremenos , Christos Dontas , Evangelos Liberopoulos

Background

Prompt initiation of lipid-lowering therapy (LLT) following acute coronary syndrome (ACS) is crucial for preventing secondary cardiovascular events. However, there are gaps in clinical implementation of the 2019 ESC/EAS guideline-recommended low-density lipoprotein cholesterol (LDL-C) goal of <55 mg/dL in patients post-ACS.

Methods

This multicenter, real-world, retrospective, 12-month study of adult patients in Greece hospitalized for ACS from September 2019 to November 2022 assessed the attainment of target LDL-C (<55 mg/dL) during the first year post-ACS. Eligible patients had elevated LDL-C at hospitalization (>130 mg/dL if LLT naïve; >100 mg/dL if on statin monotherapy; >70 mg/dL if on a statin plus ezetimibe) and ≥1 LDL-C measurement within 12 months post-ACS.

Results

Overall, 212 eligible patients of mean (SD) age 59.9 (±11.1) years were enrolled. Type 2 diabetes and hypertension were reported in 19.8 % (42/212) and 50.9 % (108/212) of patients, respectively. Median (Q1, Q3) LDL-C was 138.0 (106.5, 158.0) mg/dL at hospitalization (n = 212). In patients with LDL-C availability at 12 months posthospitalization (n = 197), median (Q1, Q3) LDL-C was 64.0 (53.0, 76.0) mg/dL, with 27.9 % of patients (55/197) attaining LDL-C <55 mg/dL. Although 73.9 % of patients (199/212) were discharged from the hospital on statin monotherapy, 50 % of patients (106/212) were receiving statin-ezetimibe LLT and 1.4 % (3/212) were receiving statin-ezetimibe-PCSK9 inhibitor LLT 12 months posthospitalization.

Conclusion

LDL-C goal attainment is suboptimal in the first year after ACS hospitalization in Greece, indicating an unmet need to improve the treatment of patients with hypercholesterolemia during the post-ACS period by optimizing lipid management through earlier LLT intensification.

背景：急性冠脉综合征（ACS）后立即开始降脂治疗（LLT）对于预防继发性心血管事件至关重要。然而，2019年ESC/EAS指南推荐的acs后患者低密度脂蛋白胆固醇（LDL-C）目标为55 mg/dL，在临床实施方面存在差距。该多中心、真实世界、回顾性、12个月的研究对2019年9月至2022年11月在希腊因ACS住院的成年患者进行了评估，评估ACS后第一年LDL-C目标（55 mg/dL）的实现情况。符合条件的患者入院时LDL-C升高(如果LLT为130 mg/dL naïve；他汀类药物单药治疗100mg /dL；[gt;70 mg/dL（如果服用他汀类药物加依折麦比），并且在acs后12个月内检测LDL-C≥1次。结果共纳入212例符合条件的患者，平均（SD）年龄59.9（±11.1）岁。2型糖尿病和高血压分别占19.8%（42/212）和50.9%（108/212）。住院时LDL-C中位数（Q1, Q3）为138.0 (106.5,158.0)mg/dL （n = 212）。在入院后12个月LDL-C可用性的患者中（n = 197），中位（Q1, Q3） LDL-C为64.0 (53.0,76.0)mg/dL， 27.9%的患者（55/197）达到LDL-C和lt；55 mg/dL。尽管73.9%的患者（199/212）接受他汀类药物单药治疗出院，但50%的患者（106/212）在住院后12个月接受他汀-依泽替米- pcsk9抑制剂LLT， 1.4%（3/212）接受他汀-依泽替米- pcsk9抑制剂LLT。结论：希腊患者在ACS住院后第一年ldl - c目标实现情况不理想，表明通过早期LLT强化优化脂质管理来改善ACS后期高胆固醇血症患者治疗的需求尚未得到满足。

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引用次数: 0

A male patient with pseudoxanthoma elasticum caused by isodisomy of chromosome 16 containing a nonsense variant of the ABCC6 gene: A quarter-century treatment experience 1例男性弹性假性黄瘤患者，由含有ABCC6基因无义变异的16号染色体同位体引起：25年的治疗经验

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-03-21 DOI: 10.1016/j.athplu.2025.03.001

Minoru Wakasa , Chihiro Nakagawa , Taka-aki Takamura , Kosuke Fujibayashi , Hironobu Akao , Michihiko Kitayama , Akira Shimizu , Yo Niida , Kouji Kajinami

Pseudoxanthoma elasticum (PXE) is a rare autosomal recessive disorder characterized by fragmentation and calcification of the elastic fibers of the skin, eyes, and various arteries with highly variable clinical expression. PXE is predominantly caused by pathogenic variants of the ABCC6 gene, which encodes the ABCC6 efflux transporter; however, the precise mechanism responsible for clinical manifestation remains unclear. We herein report the case of a male patient with PXE with premature coronary stenosis as his first presentation requiring catheter intervention, in association with typical ocular and skin lesions; the latter was confirmed histologically. A molecular analysis revealed an isodisomy of 6.8 Mb in the 16p13.11 region containing the nonsense mutation p.(Gln199Ter) in the ABCC6 gene. We also describe the 25-year clinical course of this case, while focusing on cardiovascular lesions.

弹性假性黄瘤（PXE）是一种罕见的常染色体隐性遗传病，以皮肤、眼睛和各种动脉的弹性纤维碎裂和钙化为特征，临床表现变化很大。PXE主要由编码ABCC6外排转运体的ABCC6基因的致病性变异引起；然而，导致临床表现的确切机制尚不清楚。我们在此报告一例男性PXE患者，早期冠状动脉狭窄作为他的第一个表现，需要导管介入治疗，并伴有典型的眼部和皮肤病变；后者在组织学上得到证实。分子分析显示，在ABCC6基因16p13.11区存在6.8 Mb的同位异构体，包含无义突变p.（Gln199Ter）。我们也描述了该病例25年的临床过程，同时重点关注心血管病变。

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引用次数: 0

HDL-replacement therapy: From traditional to emerging clinical applications 高密度脂蛋白替代疗法：从传统到新兴临床应用

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-03-01 DOI: 10.1016/j.athplu.2025.02.001

Cesare Riccardo Sirtori , Giulia Cincotto , Sofia Castiglione , Chiara Pavanello

The unique and multifaceted properties of high-density lipoproteins (HDL)—ranging from cholesterol efflux to anti-inflammatory, anti-oxidant, and immunomodulatory effects—have prompted their direct use, particularly in cardiovascular ischemic conditions.

Recent advances have extended the interest in HDL-based treatments to novel applications, from improving stent biocompatibility, to treatment of heart failure to central nervous system (CNS) disorders. Strategies to harness HDL's therapeutic potential have evolved from the direct use of isolated HDL in animal models to reconstituted HDL (rHDL) in humans. For these latter, the use of isolated apoA-I associated with different phospholipids has been the most frequent approach, also involving apparently beneficial mutants, such as the apo A-I Milano (AIM).

From the initial very promising results, particularly with this mutant in coronary patients, later studies have mostly been non-confirmatory, although issues such as possible inadequate dose/response and unexpected immunological properties have come to light. Most recently a study on isolated plasma HDL in coronary patients (AEGIS-II) provided overall negative findings, but a clear fall of major cardiovascular events was recorded when restricting analysis to hypercholesterolemic patients.

Emerging approaches, including gene therapy and plant-derived recombinant HDL formulations, hold promise for enhancing the accessibility and efficacy of HDL-based interventions. At this time, an improved approach to heart failure treatment also appears feasible, and a better understanding of the role played by HDL in the CNS may lead to significant improvements in the handling of some dramatic diseases at this level. While challenges persist, the evolving landscape of HDL replacement therapies offers hope for significant progress in addressing both cardiovascular and non-cardiovascular conditions.

高密度脂蛋白（HDL）的独特和多方面的特性-从胆固醇外排到抗炎、抗氧化和免疫调节作用-促使其直接使用，特别是在心血管缺血性疾病中。最近的进展将高密度脂蛋白治疗的兴趣扩展到新的应用，从改善支架生物相容性，到治疗心力衰竭到中枢神经系统（CNS）疾病。利用HDL的治疗潜力的策略已经从直接在动物模型中使用分离的HDL发展到在人体中重建HDL （rHDL）。对于后者，使用与不同磷脂相关的分离载脂蛋白A-I是最常用的方法，也涉及明显有益的突变体，如载脂蛋白A-I米兰（AIM）。从最初非常有希望的结果，特别是在冠状动脉患者中的这种突变，尽管可能的剂量/反应不足和意想不到的免疫特性等问题已经曝光，但后来的研究大多是非证实性的。最近一项对冠状动脉患者分离血浆HDL的研究（AEGIS-II）提供了总体阴性结果，但当限制分析高胆固醇血症患者时，记录了主要心血管事件的明显下降。包括基因治疗和植物衍生的重组HDL制剂在内的新兴方法有望提高基于HDL的干预措施的可及性和有效性。此时，一种改进的心力衰竭治疗方法似乎也是可行的，并且更好地了解HDL在中枢神经系统中所起的作用可能会导致在这一水平上处理一些严重疾病的显着改善。尽管挑战依然存在，高密度脂蛋白替代疗法的发展前景为解决心血管和非心血管疾病的重大进展提供了希望。

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引用次数: 0

Safety and efficacy of edoxaban monotherapy after bioabsorbable polymer everolimus-eluting stent implantation in a human-like coronary atherosclerotic porcine model 生物可吸收聚合物依维莫司洗脱支架植入人冠状动脉粥样硬化猪模型后单药依多沙班治疗的安全性和有效性

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-01-31 DOI: 10.1016/j.athplu.2025.01.002

Daisuke Kitano , Suguru Migita , Yuxin Li , Yutaka Koyama , Katsunori Fukumoto , Sayaka Shimodai-Yamada , Akira Onishi , Daiichiro Fuchimoto , Shunichi Suzuki , Yoshiyuki Nakamura , Atsushi Hirayama , Hiroyuki Hao , Yasuo Okumura

Background

The combination of antiplatelet and antithrombotic drugs increases the risk of bleeding in patients with atrial fibrillation after coronary drug-eluting stent (DES) implantation. However, the appropriateness of direct-acting oral anticoagulant (DOAC) monotherapy at the time of stent implantation remains uncertain. The objective of this study was to evaluate the safety and efficacy of DOAC monotherapy, specifically using factor Xa inhibitors such as edoxaban, in a low-density lipoprotein receptor knockout (LDL-R^−/−) miniature pig model of human-like unstable coronary plaques compared to conventional dual-antiplatelet therapy (DAPT).

Methods

We evaluated the safety and efficacy of edoxaban monotherapy in the LDL-R^−/− pig model with human-like unstable coronary plaques induced by a high-cholesterol, high-fat diet. Animals underwent DES implantation, followed by four weeks of treatment with either edoxaban monotherapy (3 mg/kg/day) or the DAPT regimen (aspirin 100 mg/day and clopidogrel 75 mg/day). Outcomes were assessed by optical coherence tomography (OCT), virtual histology intravascular ultrasound (iMap-IVUS), and histology. Key endpoints included in-stent thrombus formation, neointimal thickness, and coronary plaque composition.

Results

Edoxaban monotherapy demonstrated a significantly thinner neointimal layer (120.0 [92.5–160.0] μm vs. 210.0 [180.0–240.0] μm, p < 0.001) and smaller neointimal area (1.06 [0.82–1.46] mm² vs. 1.84 [1.61–2.24] mm², p < 0.001) compared to DAPT. Neointimal coverage, fibrin deposition, and inflammatory cell infiltration were comparable between groups. No in-stent thrombi were observed in either group. iMap-IVUS findings indicated that edoxaban monotherapy significantly suppressed the increase in lipidic and necrotic plaque area while promoting fibrotic area expansion.

Conclusions

Edoxaban monotherapy demonstrated superior efficacy in suppressing neointimal hyperplasia and stabilizing coronary plaques compared to DAPT with equivalent safety in preventing in-stent thrombus formation. These results provide important preclinical evidence supporting the potential of DOAC monotherapy as an antithrombotic strategy after DES implantation and warrant further investigation in clinical trials.

背景抗血小板和抗血栓药物联合使用会增加冠状动脉药物洗脱支架（DES）植入术后房颤患者出血的风险。然而，直接作用口服抗凝剂（DOAC）单药治疗在支架植入时的适宜性仍不确定。本研究的目的是评估DOAC单药治疗的安全性和有效性，特别是使用Xa因子抑制剂，如伊多沙班，在低密度脂蛋白受体敲除（LDL-R−/−）的小型猪模型中，与传统的双抗血小板治疗（DAPT）相比，人样不稳定冠状动脉斑块。方法在高胆固醇、高脂肪饮食诱导的具有人类样不稳定冠状动脉斑块的LDL-R - / -猪模型中，我们评估了依多沙班单药治疗的安全性和有效性。动物接受DES植入，随后接受4周的伊多沙班单药治疗（3 mg/kg/天）或DAPT方案（阿司匹林100 mg/天，氯吡格雷75 mg/天）。通过光学相干断层扫描（OCT）、血管内超声虚拟组织学（iMap-IVUS）和组织学评估结果。关键终点包括支架内血栓形成、内膜厚度和冠状动脉斑块组成。结果多沙班单药组新生内膜层明显变薄(120.0 [92.5 ~ 160.0]μm vs. 210.0 [180.0 ~ 240.0] μm, p <；0.001)和较小的内膜面积(1.06 [0.82-1.46]mm2 vs. 1.84 [1.61-2.24] mm2, p <；0.001)，与DAPT相比。新生内膜覆盖、纤维蛋白沉积和炎症细胞浸润在两组间具有可比性。两组均未见支架内血栓形成。iMap-IVUS结果显示，伊多沙班单药治疗可显著抑制脂质斑块和坏死斑块面积的增加，同时促进纤维化区域的扩张。结论与DAPT相比，多沙班单药治疗在抑制新内膜增生和稳定冠状动脉斑块方面具有更强的疗效，在预防支架内血栓形成方面具有同等的安全性。这些结果提供了重要的临床前证据，支持DOAC单药治疗作为DES植入后抗血栓策略的潜力，值得在临床试验中进一步研究。

{"title":"Safety and efficacy of edoxaban monotherapy after bioabsorbable polymer everolimus-eluting stent implantation in a human-like coronary atherosclerotic porcine model","authors":"Daisuke Kitano , Suguru Migita , Yuxin Li , Yutaka Koyama , Katsunori Fukumoto , Sayaka Shimodai-Yamada , Akira Onishi , Daiichiro Fuchimoto , Shunichi Suzuki , Yoshiyuki Nakamura , Atsushi Hirayama , Hiroyuki Hao , Yasuo Okumura","doi":"10.1016/j.athplu.2025.01.002","DOIUrl":"10.1016/j.athplu.2025.01.002","url":null,"abstract":"<div><h3>Background</h3><div>The combination of antiplatelet and antithrombotic drugs increases the risk of bleeding in patients with atrial fibrillation after coronary drug-eluting stent (DES) implantation. However, the appropriateness of direct-acting oral anticoagulant (DOAC) monotherapy at the time of stent implantation remains uncertain. The objective of this study was to evaluate the safety and efficacy of DOAC monotherapy, specifically using factor Xa inhibitors such as edoxaban, in a low-density lipoprotein receptor knockout (LDL-R<sup>−/−</sup>) miniature pig model of human-like unstable coronary plaques compared to conventional dual-antiplatelet therapy (DAPT).</div></div><div><h3>Methods</h3><div>We evaluated the safety and efficacy of edoxaban monotherapy in the LDL-R<sup>−/−</sup> pig model with human-like unstable coronary plaques induced by a high-cholesterol, high-fat diet. Animals underwent DES implantation, followed by four weeks of treatment with either edoxaban monotherapy (3 mg/kg/day) or the DAPT regimen (aspirin 100 mg/day and clopidogrel 75 mg/day). Outcomes were assessed by optical coherence tomography (OCT), virtual histology intravascular ultrasound (iMap-IVUS), and histology. Key endpoints included in-stent thrombus formation, neointimal thickness, and coronary plaque composition.</div></div><div><h3>Results</h3><div>Edoxaban monotherapy demonstrated a significantly thinner neointimal layer (120.0 [92.5–160.0] μm vs. 210.0 [180.0–240.0] μm, <em>p</em> < 0.001) and smaller neointimal area (1.06 [0.82–1.46] mm<sup>2</sup> vs. 1.84 [1.61–2.24] mm<sup>2</sup>, <em>p</em> < 0.001) compared to DAPT. Neointimal coverage, fibrin deposition, and inflammatory cell infiltration were comparable between groups. No in-stent thrombi were observed in either group. iMap-IVUS findings indicated that edoxaban monotherapy significantly suppressed the increase in lipidic and necrotic plaque area while promoting fibrotic area expansion.</div></div><div><h3>Conclusions</h3><div>Edoxaban monotherapy demonstrated superior efficacy in suppressing neointimal hyperplasia and stabilizing coronary plaques compared to DAPT with equivalent safety in preventing in-stent thrombus formation. These results provide important preclinical evidence supporting the potential of DOAC monotherapy as an antithrombotic strategy after DES implantation and warrant further investigation in clinical trials.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"59 ","pages":"Pages 59-67"},"PeriodicalIF":1.4,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143263756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

“Inclisiran: Early LDL-C target achievement in a real-life population” “Inclisiran：在现实生活人群中早期实现LDL-C目标”

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-01-28 DOI: 10.1016/j.athplu.2025.01.001

Francesco Briani , Mauro Bagli , Gabriele Venturi , Francesco Bacchion , Antonio Mugnolo

Background and objectives

Elevated low-density lipoprotein cholesterol (LDL-C) levels are associated with atherosclerotic cardiovascular diseases. Inclisiran, a small interfering RNA, has been observed to effectively and sustainably reduce LDL-C in large randomized controlled trials (RCTs); however, real-world data on its short-term efficacy and use are limited. This study aims to assess the efficacy and safety of inclisiran in a real-life population within one month from the first administration.

Methods

This observational, single-center, retrospective cohort study included patients affected by dyslipidemia who could not achieve their LDL-C target despite a maximum tolerated oral lipid-lowering therapy (LLT). 284 mg Inclisiran was subcutaneously administered. Blood samples were collected before the inclisiran administration and at week and one month afterward with the aim toevaluate achievement of LDL-C targets at these time intervals (primary endpoint) and reduction in LDL-C levels (secondary endpoint).

Results

From September 2022 to December 2023, inclisiran was administered to 33 patients at Mater Salutis Hospital. After exclusion of two patients due to statin therapy modification or discontinuation during follow-up, a final number of 31 patients were included. At a median follow-up of 32 (IQ_1-3 30–37) days, 21 (67.7 %) patients reached their LDL-C target (primary endpoint). At 7 days, LDL-C mean value decreased from 123.6 ± 42.1 mg/dl to 97.9 ± 53.6 mg/dl, (p < 0.001), with a 29.9 ± 20.6 % reduction. At 32 days, LDL-C mean value declined to 58.5 ± 42.8 mg/dl (p < 0.001), with a 56.9 ± 20.9 % reduction.

Conclusion

In a real-life single center population, inclisiran safely led to LDL-C target achievement within one month. Significantly reduction of LDL-C levels were already present in the early days after the first administration.

背景和目的低密度脂蛋白胆固醇（LDL-C）水平升高与动脉粥样硬化性心血管疾病有关。Inclisiran是一种小干扰RNA，在大型随机对照试验（RCTs）中被观察到有效且持续地降低LDL-C；然而，关于其短期疗效和使用的实际数据有限。本研究旨在评估inclisiran在首次给药后一个月内对真实人群的有效性和安全性。方法：这项观察性、单中心、回顾性队列研究纳入了尽管接受了最大耐受口服降脂治疗（LLT），但仍无法达到LDL-C目标的血脂异常患者。皮下给药Inclisiran 284 mg。在给药前和给药后一周和一个月采集血样，目的是评估在这些时间间隔内LDL-C目标的实现情况（主要终点）和LDL-C水平的降低情况（次要终点）。结果从2022年9月至2023年12月，我院共收治33例患者。在排除了两名因他汀类药物治疗改变或停药的患者后，最终纳入了31名患者。中位随访32天（IQ1-3 - 30-37）， 21例（67.7%）患者达到LDL-C目标（主要终点）。第7天，LDL-C平均值从123.6±42.1 mg/dl降至97.9±53.6 mg/dl, (p <；0.001)，降低29.9±20.6%。第32天，LDL-C平均值降至58.5±42.8 mg/dl (p <；0.001)，降低56.9±20.9%。结论在现实生活中的单中心人群中，inclisiran可以安全地在一个月内达到LDL-C目标。在第一次给药后的早期，LDL-C水平已经显著降低。

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引用次数: 0

Anti-atherosclerotic effects of natural compounds targeting lipid metabolism and inflammation: Focus on PPARs, LXRs, and PCSK9 针对脂质代谢和炎症的天然化合物的抗动脉粥样硬化作用：关注PPARs， LXRs和PCSK9

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2024-12-24 DOI: 10.1016/j.athplu.2024.12.004

Marcella Palumbo , Martina Ugolotti , Francesca Zimetti , Maria Pia Adorni

A large body of evidence has shown that modulation of the nuclear receptors peroxisome proliferator-activated receptors (PPARs), the liver X receptors (LXRs), the proprotein convertase subtilisin/kexin type 9 (PCSK9) and inflammatory processes by natural compounds has hypolipidemic and anti-atherosclerotic effects. These beneficial outcomes are certainly related to the crucial function of these targets in maintaining cholesterol homeostasis and regulating systemic inflammation. Currently, the therapeutic scenario for cardiovascular diseases (CVD) offers a plethora of widely validated and functional pharmacological treatments to improve the health status of patients. However, patients are increasingly sceptical of pharmacological treatments which are often associated with moderate to severe side effects. The aim of our review is to provide a collection of the most recent scientific evidence on the most common phytochemicals, used for centuries in the Mediterranean diet and traditional chinese medicine that act on these key regulators of cholesterol homeostasis and systemic inflammation, which could constitute important tools for CVD management.

大量证据表明，天然化合物对核受体过氧化物酶体增殖激活受体（PPARs）、肝脏X受体（LXRs）、枯草杆菌素/酮素9型蛋白转化酶（PCSK9）和炎症过程的调节具有降血脂和抗动脉粥样硬化作用。这些有益的结果肯定与这些靶点在维持胆固醇稳态和调节全身炎症方面的关键功能有关。目前，心血管疾病（CVD）的治疗方案提供了大量广泛验证和功能性的药物治疗来改善患者的健康状况。然而，患者越来越怀疑药物治疗，这往往与中度到严重的副作用有关。我们综述的目的是收集最新的科学证据，证明几个世纪以来在地中海饮食和传统中医中使用的最常见的植物化学物质对胆固醇稳态和全身炎症的关键调节作用，这可能构成心血管疾病管理的重要工具。

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引用次数: 0

Impact of NAFLD-related SNPs on the carotid atherosclerosis development; a five-year prospective observational study nafld相关snp对颈动脉粥样硬化发展的影响一项为期五年的前瞻性观察研究。

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2024-12-14 DOI: 10.1016/j.athplu.2024.12.003

Hiroaki Ikezaki , Ryoko Nakashima , Yuji Matsumoto , Azusa Ohta , Sho Yamasaki , Satoshi Hiramine , Koji Takayama , Eiichi Ogawa , Masayuki Murata , Norihiro Furusyo , Jun Hayashi , Nobuyuki Shimono , Ernst J. Schaefer

Background and aims

The prevalence of metabolic dysfunction associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), has become a significant public health concern with an increased atherosclerotic cardiovascular disease risk. This study investigates the impact of NAFLD-related single nucleotide polymorphisms (SNPs) on carotid atherosclerosis development in a Japanese population without diabetes, dyslipidemia, and hypertension.

Methods

The prospective observational study, part of the Kyushu and Okinawa Population Study (KOPS), included 945 participants (median age 55 [47, 63]) without carotid atherosclerosis, increased alcohol intake, diabetes, dyslipidemia, hypertension, or chronic hepatitis at baseline. NAFLD-related SNPs (GCKR, NCAN, and PNPLA3) were genotyped, and carotid intima-media thickness (cIMT) was measured using ultrasonography. Univariate and multivariate regression analyses were performed to assess the association of NAFLD-related SNPs on newly developed carotid atherosclerosis over five years.

Results

After five years, 125 (13.2 %) participants developed carotid atherosclerosis. The NCAN (rs2228603) T allele was associated with a lower incidence rate of carotid atherosclerosis (4.7 % in NCAN CT/TT genotype vs. 13.9 % in CC genotype; p = 0.04), and NCAN T allele carriers exhibited a favorable lipid profile. These associations were not altered by either recruiting area or obese. The GCKR T allele and PNPLA3 C allele were associated with low carotid atherosclerosis development rates but were not significant.

Conclusions

Our results suggested that some NAFLD-related SNPs may influence atherosclerosis through lipid metabolism among Japanese individuals without metabolic syndrome.

背景和目的：代谢功能障碍相关性脂肪性肝病（MASLD），以前称为非酒精性脂肪肝（NAFLD），其发病率已成为一个重要的公共卫生问题，并增加了动脉粥样硬化性心血管疾病的风险。本研究调查了在没有糖尿病、血脂异常和高血压的日本人群中，非酒精性脂肪肝相关单核苷酸多态性（SNPs）对颈动脉粥样硬化发展的影响：这项前瞻性观察研究是九州和冲绳人口研究（KOPS）的一部分，共纳入了 945 名参与者（中位年龄 55 [47, 63]），他们基线时没有颈动脉粥样硬化、酒精摄入增加、糖尿病、血脂异常、高血压或慢性肝炎。对非酒精性脂肪肝相关的 SNPs（GCKR、NCAN 和 PNPLA3）进行了基因分型，并使用超声波测量了颈动脉内膜中层厚度（cIMT）。通过单变量和多变量回归分析，评估非酒精性脂肪肝相关SNPs与五年内新发颈动脉粥样硬化的关系：结果：五年后，125名参与者（13.2%）出现了颈动脉粥样硬化。NCAN（rs2228603）T等位基因与较低的颈动脉粥样硬化发病率相关（NCAN CT/TT基因型为4.7%，CC基因型为13.9%；P = 0.04），NCAN T等位基因携带者的血脂状况良好。这些关联并不因招募地区或肥胖而改变。GCKR T等位基因和PNPLA3 C等位基因与低颈动脉粥样硬化发病率相关，但不显著：我们的研究结果表明，在没有代谢综合征的日本人中，一些与非酒精性脂肪肝相关的 SNPs 可能会通过脂质代谢影响动脉粥样硬化。

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引用次数: 0

HDL-associated vitamin D binding protein levels are inversely associated with necrotic plaque burden in psoriasis 高密度脂蛋白相关的维生素D结合蛋白水平与牛皮癣坏死斑块负荷呈负相关。

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2024-12-13 DOI: 10.1016/j.athplu.2024.12.002

M.P. Playford , H. Li , A.K. Dey , E.M. Florida , H.L. Teague , S.M. Gordon , N.N. Mehta

Background and aims

Vitamin D binding protein (DBP) serves a dual function as a vitamin D carrier and actin scavenger. Free DBP is present in high concentrations in serum, while a smaller pool is bound to lipoproteins like HDL and VLDL. The role of DBP's interaction with lipoproteins remains unclear. Given that HDL has been proposed to have both atheroprotective and anti-inflammatory properties, we sought to compare whether HDL-associated DBP and/or total serum DBP could serve as useful biomarkers for assessing disease severity in psoriasis and cardiovascular disease.

Methods

Psoriasis (PSO) patients (N = 83), which were part of a prospective, observational cohort and non-psoriasis (non-PSO) subjects (n = 35) underwent blood collection for HDL purification by liquid chromatography and CCTA scans to assess coronary plaque burden. Serum and HDL-bound DBP levels were measured by ELISA.

Results

The psoriasis cohort was middle-aged (mean ± IQR: 50 (38–59), predominantly male (n = 55, 66 %) and had moderate-to-severe skin disease [psoriasis area severity index score, PASI score, med (IQR): 9.6 (6–18.3)]. Consistent with our previous reports, PSO patients had significantly higher Framingham Risk Score (FRS), high sensitivity C-reactive protein (hs-CRP), Body Mass Index (BMI), insulin resistance (HOMA-IR) and total coronary plaque burden, driven by the rupture-prone non-calcified necrotic core. However, while the concentration of serum DBP (S-DBP) between PSO and non-PSO was unchanged (PSO: 177.80 (125.77–250.99) vs non-PSO: 177.74 (104.32–254.04), the concentration of DBP associated with HDL (HDL-DBP) was decreased in psoriatics (PSO μg/ml: 1.38 (0.64–2.75) vs non-PSO: 1.72 (1.18–3.90). Although both S-DBP and HDL-DBP levels showed inverse correlations with a measure of skin disease severity (PASI) (S-DBP, Rho = −0.022 vs HDL-DBP, Rho = −113), only HDL-DBP exhibited an inverse relationship with necrotic plaque burden [Rho −0.226, p = 0.085 vs S-DBP (0.041, p = 0.76)]. This relationship was strengthened after adjusting for traditional cardiovascular risk factors such as age and sex (β = −0.237, p = 0.045), FRS (β = −0.295, p = 0.033) and including biological treatment and HDL-cholesterol (β = −0.213, p = 0.048).

Conclusions

In conclusion, we found HDL-DBP levels may better capture the severity of psoriatic disease and association with cardiovascular risk factors than S-DBP.

背景与目的：维生素D结合蛋白（DBP）具有维生素D载体和肌动蛋白清除剂的双重功能。游离DBP在血清中以高浓度存在，而较小的池与HDL和VLDL等脂蛋白结合。DBP与脂蛋白相互作用的作用尚不清楚。鉴于HDL已被提出具有动脉粥样硬化保护和抗炎特性，我们试图比较HDL相关舒张压和/或总血清舒张压是否可以作为评估牛皮癣和心血管疾病严重程度的有用生物标志物。方法：作为前瞻性观察队列的一部分，银屑病（PSO）患者（N = 83）和非银屑病（non-PSO）受试者（N = 35）采集血液，通过液相色谱和CCTA扫描进行HDL纯化，以评估冠状动脉斑块负担。ELISA法测定血清及高密度脂蛋白结合DBP水平。结果：银屑病队列为中年人（平均±IQR: 50(38-59)），以男性为主（n = 55,66 %），患有中重度皮肤病[银屑病区域严重程度指数评分，PASI评分，med (IQR): 9.6(6-18.3)]。与我们之前的报道一致，PSO患者有明显更高的弗雷明汉风险评分（FRS）、高敏c反应蛋白（hs-CRP）、体重指数（BMI）、胰岛素抵抗（HOMA-IR）和总冠状动脉斑块负担，这是由易破裂的非钙化坏死核心驱动的。然而，银屑病患者血清DBP （S-DBP）与非PSO之间的差异无显著性(PSO: 177.80 (125.77-250.99) vs非PSO: 177.74(104.32-254.04)，而与HDL相关的DBP （HDL-DBP）浓度在银屑病患者中有所降低(PSO μg/ml: 1.38 （0.64-2.75) vs非PSO: 1.72(1.18-3.90)）。尽管S-DBP和HDL-DBP水平均与皮肤病严重程度（PASI）呈负相关（S-DBP, Rho = -0.022 vs HDL-DBP, Rho = -113），但只有HDL-DBP与坏死斑块负担呈负相关[Rho -0.226, p = 0.085 vs S-DBP (0.041, p = 0.76)]。在校正了传统的心血管危险因素如年龄和性别（β = -0.237, p = 0.045）、FRS （β = -0.295, p = 0.033）以及生物治疗和高密度脂蛋白胆固醇（β = -0.213, p = 0.048）后，这种关系得到加强。结论：总之，我们发现HDL-DBP水平比S-DBP水平更能反映银屑病的严重程度及其与心血管危险因素的关系。

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引用次数: 0

Disparities in patterns and outcomes of dyslipidemic patients with acute coronary syndrome: A tertiary cardiac center registry 急性冠状动脉综合征的血脂异常患者的模式和结果的差异：三级心脏中心登记。

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2024-12-12 DOI: 10.1016/j.athplu.2024.11.004

Hesham Taha , Mohammad Alshehri , Hossam El-Hosary , Abdalla Elagha , Hosam Mahrous , Mirna Shaker , Omar Younis , Mohamed Saad

引用次数: 0