Atherosclerosis最新文献_第8页

The association between atherogenic index of plasma and risk of preeclampsia: a prospective cohort study 血浆动脉粥样硬化指数与子痫前期风险之间的关系：一项前瞻性队列研究。

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2025-10-10 DOI: 10.1016/j.atherosclerosis.2025.120545

Doudou Zhao , Jie Chen , Xiayang Li , Yishuai Huang , Yu Zhang , Fuyang Zhao , Li Shan , Yang Mi , Pengfei Qu , Lei Shang

Background and aims

The atherogenic index of plasma (AIP) has been linked to hypertension in general populations. However, the existing evidence concerning its association with preeclampsia risk remains limited. This study aimed to assess the relationship between first-trimester AIP level and preeclampsia risk.

Methods

6028 singleton pregnant women from a birth cohort, all under 14 weeks of gestation and without a history of hypertension, were included. AIP was calculated as log₁₀ (triglycerides/high-density lipoprotein cholesterol). Generalized linear models and restricted cubic spline regression were utilized to estimate the associations between AIP and preeclampsia risk. A random forest model was employed to determine the relative importance of parameters for predicting preeclampsia risk.

Results

235 (3.90%) incident preeclampsia cases were confirmed. A linear relationship was found between AIP and preeclampsia risk, and each 1-standard deviation increase in AIP was associated with a 21% higher risk of preeclampsia (RR: 1.21, 95% CI: 1.06–1.38). A significant interaction was identified between AIP and uric acid (UA) level (P for interaction = 0.009). Elevated AIP was linked to an increased preeclampsia risk (RR: 1.32, 95% CI: 1.13–1.54) when UA level exceeded 198 μmol/L, and the highest combined level indicated the greatest risk. Moreover, AIP was identified as the strongest predictor among all variables in the prediction model.

Conclusions

Elevated first-trimester AIP was associated with an increased preeclampsia risk, particularly at the higher UA level. These findings highlight the clinical significance of pro-atherogenic dyslipidemia as both a risk marker and a potential target for early screening in preeclampsia prevention strategies.

背景和目的：血浆动脉粥样硬化指数（AIP）与普通人群的高血压有关。然而，关于其与先兆子痫风险相关的现有证据仍然有限。本研究旨在评估妊娠早期AIP水平与子痫前期风险之间的关系。方法：来自出生队列的6028名单胎孕妇，均在妊娠14周以下，无高血压病史。AIP计算为log10（甘油三酯/高密度脂蛋白胆固醇）。使用广义线性模型和受限三次样条回归来估计AIP与子痫前期风险之间的关系。采用随机森林模型确定预测子痫前期风险参数的相对重要性。结果：确诊子痫前期235例（3.90%）。AIP与子痫前期风险呈线性关系，AIP每增加1个标准差，子痫前期风险增加21% （RR: 1.21, 95% CI: 1.06-1.38）。AIP与尿酸（UA）水平之间存在显著交互作用（交互作用P = 0.009）。当UA水平超过198 μmol/L时，AIP升高与子痫前期风险增加相关（RR: 1.32, 95% CI: 1.13 ~ 1.54），且综合水平越高风险越大。在预测模型的所有变量中，AIP被认为是最强的预测因子。结论：妊娠早期AIP升高与子痫前期风险增加有关，特别是在UA水平较高时。这些发现强调了促动脉粥样硬化性血脂异常作为子痫前期预防策略早期筛查的风险标志和潜在目标的临床意义。

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引用次数: 0

Zbp1 promotes atherosclerosis and lesion necrosis in mice Zbp1促进小鼠动脉粥样硬化和病变坏死。

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2025-10-09 DOI: 10.1016/j.atherosclerosis.2025.120542

Juying Han , Emmanuel Opoku , Gregory Brubaker , Jonathan D. Smith

Background and aims

An AKRxDBA/2 mouse strain intercross identified an atherosclerosis modifier gene within a small region on chromosome 2, containing only three protein coding genes, including Z-DNA binding protein 1 (Zbp1), which plays a role in non-canonical necroptosis. We aimed to determine if knockout (KO) of Zpb1 decreased lesion and necrotic areas in mice.

Methods

Zpb1 isoform specific expression was assessed by RNAseq in mouse macrophages and aortic arches. Necroptosis was assessed in cultured mouse macrophages. Hyperlipidemia was induced by weekly injection of an antisense oligonucleotide targeting the mouse LDL receptor gene, combined with feeding a Western-type diet. Lesions were assessed in the aortic root and brachiocephalic artery in both sexes separately and after adjusting for sex in combined analyses.

Results

Both AKR and DBA/2 strains express two isoforms of Zbp1 mRNA with higher expression in the DBA/2 atherosclerosis-sensitive strain. Zbp1 KO and wildtype (WT) macrophages were equally susceptible to canonical and non-canonical necroptosis. There were some sex specific effects of the KO in body weight, organ weights, and plasma cholesterol values. In both sexes, KO mice trended towards, or had significantly smaller, lesion areas and necrotic cores, which were significant in combined sex analyses. Lesion cell compositions were qualitatively similar in KO and WT mice.

Conclusions

Zbp1 is an atherosclerosis modifier gene, similar to the canonical necroptosis genes Ripk1 and Mlkl. Higher expression of Zbp1 in DBA/2 mice may play a role in this strain having the largest lesions of all strains tested in the Apoe-deficient background.

背景与目的：一种AKRxDBA/2小鼠菌株在2号染色体的一个小区域内发现了一个动脉粥样硬化修饰基因，该基因仅包含3个蛋白质编码基因，其中包括Z-DNA结合蛋白1 (Zbp1)，该基因在非典型坏死性坏死中起作用。我们的目的是确定敲除（KO） Zpb1是否能减少小鼠的病变和坏死区域。方法：采用RNAseq法检测Zpb1亚型在小鼠巨噬细胞和主动脉弓中的特异性表达。在培养的小鼠巨噬细胞中评估坏死性下垂。通过每周注射一种靶向小鼠LDL受体基因的反义寡核苷酸，结合饲喂西式饮食诱导高脂血症。分别评估男女主动脉根部和头臂动脉的病变，并在合并分析中调整性别。结果：AKR和DBA/2菌株均表达Zbp1 mRNA的两种亚型，其中DBA/2动脉粥样硬化敏感菌株表达量较高。Zbp1 KO和野生型（WT）巨噬细胞对典型和非典型坏死下垂同样敏感。KO在体重、器官重量和血浆胆固醇值方面有一些性别特异性影响。在两性中，KO小鼠趋向于或具有明显较小的病变区域和坏死核心，这在合并性别分析中是显著的。KO和WT小鼠的病变细胞组成在质量上相似。结论：Zbp1是一种动脉粥样硬化修饰基因，类似于典型的坏死性坏死基因Ripk1和Mlkl。Zbp1在DBA/2小鼠中的高表达可能在该菌株在apoe缺乏背景下具有最大病变的所有菌株中发挥作用。

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引用次数: 0

Atherogenic responsibility of lipoprotein (a) and other apolipoprotein B-containing lipoproteins in acute coronary syndrome 脂蛋白(a)和其他含载脂蛋白b的脂蛋白在急性冠状动脉综合征中的致动脉粥样硬化作用。

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2025-10-09 DOI: 10.1016/j.atherosclerosis.2025.120544

Antonio Meseguer-Hernández , Francisco Buendía-Santiago , José Manuel Andreu-Cayuelas , Jaime Merino-Romero , María Isabel Baños-Maturano , Leticia Risco-Eres , María Belén Villamarín-Heredia , Bettina De Berardinis , Eloy Yordano Mite-Salazar , Lidia Martínez-Gascón , Eva Pérez-Fernández , José García-Gómez , Leticia Jaulent-Huertas , José Abellán-Huerta , Derek Dau-Villarreal , Rosario Mármol-Lozano , Juan Antonio Castillo-Moreno

Background and aims

The atherogenicity of a lipoprotein (a) particle [Lp(a)] appears to be at least 5 times higher than that of apolipoprotein B (apoB)-containing lipoproteins other than Lp(a) [non-Lp(a) apoB]. The non-Lp(a) apoB/Lp(a) ratio could be considered an indicator of the relative atherogenic contribution of each lipoprotein group. Our aim was to evaluate the non-Lp(a) apoB/Lp(a) ratio in patients with acute coronary syndrome (ACS) and the clinical features associated with this ratio.

Methods

Observational study of hospitalised patients with ACS and obstructive coronary artery disease, in whom the molar concentration (nmol/l) of apoB and Lp(a) was determined. Non-Lp(a) apoB was calculated by subtracting Lp(a) from apoB, as well as the ratio of non-Lp(a) apoB/Lp(a), which, depending on whether it was >5 or ≤5, was considered suggestive of greater atherogenic liability of non-Lp(a) apoB or Lp(a), respectively.

Results

We included 420 patients (22.4 % female; 65.5 ± 12.0 years). Lp(a) was ≤125 nmol/L in 301 (71.7 %), in all of them the non-Lp(a) apoB/Lp(a) ratio was >5. On the other hand, Lp(a) was >125 nmol/L in 119 patients (28.3 %) and, in this group, the non-Lp(a) apoB/Lp(a) ratio was ≤5 in 47 (39.5 %). In contrast to Lp(a) levels >125 nmol/l, non-Lp(a) apoB/Lp(a) ratio ≤5 was independently associated with multivessel coronary artery disease (OR = 2.317; CI95 %, 1.051–5109; p = 0.037).

Conclusions

In patients with ACS, even those with elevated Lp(a), a non-Lp(a) apoB/Lp(a) ratio >5 prevails, suggesting greater atherogenic contribution of non-Lp(a) apoB. The predominance of Lp(a) atherogenic responsibility is associated with multivessel coronary artery disease.

背景和目的：脂蛋白(a)颗粒[Lp(a)]的动脉粥样硬化性似乎比含载脂蛋白B （apoB）的脂蛋白（非Lp(a) apoB）高出至少5倍。非Lp(a) apoB/Lp(a)比率可以被认为是每个脂蛋白组相对致动脉粥样硬化贡献的指标。我们的目的是评估急性冠脉综合征（ACS）患者的非Lp(a) apoB/Lp(a)比率以及与该比率相关的临床特征。方法：对ACS合并阻塞性冠状动脉疾病住院患者进行观察性研究，测定其载脂蛋白ob和脂蛋白a的摩尔浓度（nmol/l）。通过apoB减去Lp(a)来计算非Lp(a) apoB，以及非Lp(a) apoB/Lp(a)的比值，该比值取决于其是否为bbbb5或≤5，分别被认为是非Lp(a) apoB或Lp(a)具有更大的动脉粥样硬化易损性。结果：纳入420例患者（女性22.4%;65.5±12.0岁）。其中Lp(a)≤125 nmol/L的有301例（71.7%），非Lp(a) apoB/Lp(a)比值均为bb0.5。另一方面，119例（28.3%）患者的Lp(a)为bb0 125 nmol/L， 47例（39.5%）患者的非Lp(a) apoB/Lp(a)比值≤5。与Lp(a)水平>125 nmol/l相比，非Lp(a) apoB/Lp(a)比值≤5与多支冠状动脉疾病独立相关（OR = 2.317; CI95 %, 1.051-5109; p = 0.037）。结论：在ACS患者中，即使是Lp(a)升高的患者，非Lp(a) apoB/Lp(a)比值bbb50也普遍存在，表明非Lp(a) apoB对动脉粥样硬化的贡献更大。Lp(a)动脉粥样硬化的优势与多支冠状动脉疾病有关。

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引用次数: 0

Associations between ideal cardiovascular health metrics and lipoprotein subclasses and atherogenic indices: A cross-sectional study of middle-to older-aged adults 理想心血管健康指标与脂蛋白亚类和动脉粥样硬化指数之间的关系：一项针对中老年成年人的横断面研究

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2025-10-09 DOI: 10.1016/j.atherosclerosis.2025.120543

Duong T. Luong , Seán R. Millar , James D. Otvos , Ivan J. Perry , Catherine M. Phillips

Background and aims

The American Heart Association ideal cardiovascular health (CVH) score aims, through positive health promotion, to improve cardiovascular health. Lipoprotein particles and atherogenic indices can provide better cardiovascular disease risk prediction than traditional lipid measures. Yet, ideal CVH score associations with intermediate disease markers remains under-researched. This study addressed this gap by investigating CVH score relationships with lipoprotein particle subclass concentrations and atherogenic risk indices.

Methods

This was a cross-sectional study of 1216 middle-to older-aged men and women randomly selected from a large primary care centre. Individual participant CVH metrics (smoking, BMI, physical activity, diet, blood pressure, blood glucose and cholesterol) were derived from validated questionnaires, clinical assessment and biochemistry tests. Lipoprotein particle subclass concentrations and size were determined using nuclear magnetic resonance spectroscopy. Atherogenic risk indices were derived from lipid/lipoprotein measures. Linear regression analyses examined CVH score associations with lipoprotein biomarkers and atherogenic indices.

Results

In fully adjusted models, higher scores were associated with smaller VLDL and larger LDL and HDL particle size, less large and medium VLDL, total LDL and small LDL particles, more large HDL particles, and lower lipoprotein-related insulin resistance and atherogenic risk index scores. In models which examined these variable associations across CVH score quintiles, significant dose-response relationships were observed (p trend <0.001 for all).

Conclusions

Higher CVH scores were associated with more favourable lipoprotein subclass concentrations and atherogenic risk profiles, highlighting the score’s potential usefulness as a tool for assessing atherogenic risk and the importance of improving overall cardiovascular health.

背景与目的：美国心脏协会理想心血管健康（CVH）评分旨在通过积极的健康促进来改善心血管健康。与传统的血脂指标相比，脂蛋白颗粒和动脉粥样硬化指标可以更好地预测心血管疾病的风险。然而，理想的CVH评分与中间疾病标志物的关联仍有待研究。本研究通过调查CVH评分与脂蛋白颗粒亚类浓度和动脉粥样硬化风险指数的关系来解决这一空白。方法：这是一项横断面研究，从一个大型初级保健中心随机选择1216名中老年男性和女性。个体参与者CVH指标（吸烟、BMI、体力活动、饮食、血压、血糖和胆固醇）来自有效的问卷调查、临床评估和生物化学测试。用核磁共振波谱法测定脂蛋白颗粒亚类浓度和大小。动脉粥样硬化风险指数来源于脂质/脂蛋白测量。线性回归分析检验了CVH评分与脂蛋白生物标志物和动脉粥样硬化指数的相关性。结果：在完全调整后的模型中，得分越高，VLDL越小，LDL和HDL粒径越大，VLDL大、中、总LDL和小LDL颗粒越少，HDL大颗粒越多，脂蛋白相关胰岛素抵抗和动脉粥样硬化风险指数得分越低。在检查CVH评分五分之一的这些变量关联的模型中，观察到显著的剂量-反应关系（p趋势）。结论：CVH评分越高，脂蛋白亚类浓度越有利，动脉粥样硬化风险概况越好，突出了该评分作为评估动脉粥样硬化风险和改善整体心血管健康重要性的工具的潜在有用性。

{"title":"Associations between ideal cardiovascular health metrics and lipoprotein subclasses and atherogenic indices: A cross-sectional study of middle-to older-aged adults","authors":"Duong T. Luong , Seán R. Millar , James D. Otvos , Ivan J. Perry , Catherine M. Phillips","doi":"10.1016/j.atherosclerosis.2025.120543","DOIUrl":"10.1016/j.atherosclerosis.2025.120543","url":null,"abstract":"<div><h3>Background and aims</h3><div>The American Heart Association ideal cardiovascular health (CVH) score aims, through positive health promotion, to improve cardiovascular health. Lipoprotein particles and atherogenic indices can provide better cardiovascular disease risk prediction than traditional lipid measures. Yet, ideal CVH score associations with intermediate disease markers remains under-researched. This study addressed this gap by investigating CVH score relationships with lipoprotein particle subclass concentrations and atherogenic risk indices.</div></div><div><h3>Methods</h3><div>This was a cross-sectional study of 1216 middle-to older-aged men and women randomly selected from a large primary care centre. Individual participant CVH metrics (smoking, BMI, physical activity, diet, blood pressure, blood glucose and cholesterol) were derived from validated questionnaires, clinical assessment and biochemistry tests. Lipoprotein particle subclass concentrations and size were determined using nuclear magnetic resonance spectroscopy. Atherogenic risk indices were derived from lipid/lipoprotein measures. Linear regression analyses examined CVH score associations with lipoprotein biomarkers and atherogenic indices.</div></div><div><h3>Results</h3><div>In fully adjusted models, higher scores were associated with smaller VLDL and larger LDL and HDL particle size, less large and medium VLDL, total LDL and small LDL particles, more large HDL particles, and lower lipoprotein-related insulin resistance and atherogenic risk index scores. In models which examined these variable associations across CVH score quintiles, significant dose-response relationships were observed (<em>p</em> trend <0.001 for all).</div></div><div><h3>Conclusions</h3><div>Higher CVH scores were associated with more favourable lipoprotein subclass concentrations and atherogenic risk profiles, highlighting the score’s potential usefulness as a tool for assessing atherogenic risk and the importance of improving overall cardiovascular health.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"410 ","pages":"Article 120543"},"PeriodicalIF":5.7,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Coronary lipid burden indices predict non-culprit major adverse cardiac events independently of novel LDL estimates: Insights from the LRP study 冠状动脉脂质负担指数独立于新的LDL估计预测非罪魁祸首主要不良心脏事件：来自LRP研究的见解

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2025-10-06 DOI: 10.1016/j.atherosclerosis.2025.120525

Kayode O. Kuku , Hector M. Garcia-Garcia , Gary S. Mintz , Priti Shah , Stephen Sum , Carlo Di Mario , Adriaan A. Voors , Joanna J. Wykrzykowska , Ron Waksman , the LRP Investigators

Background and aims

Coronary Lipid Burden measured by NIRS-IVUS (maxLCBI4mm > 400) predicts non-culprit major adverse cardiac events (MACE) but has shown weak correlation with traditional low-density lipoprotein (LDL) measures. We derived novel LDL-cholesterol (LDL-C) and LDL-triglyceride (eLDL-TG) estimates and evaluated their relationship with maxLCBI4mm.

Method

In the Lipid-Rich Plaque study (2014–2016), participants, LDL-C, and eLDL-TG were estimated with National Institutes of Health equations, and coronary segment maxLCBI_4mm was quantified by an independent Core lab. Linear regression models adjusted for possible confounders were used to assess the relationship between the LDL estimates and maxLCBI4mm. Kaplan–Meier curves evaluated non-culprit MACE rates by maxLCBI_4mm ≤ 400 vs. >400, stratified by LDL-C (≥/<70 mg/dL) and eLDL-TG (≥/<60th percentile). Cox proportional hazards model assessed the risk of non-culprit MACE by maxLCBI_4mm and the effect of LDL estimate groups.

Results

In the 626 evaluable patients (410 with maxLCBI_4mm ≤ 400 and 216 > 400), there was no association between baseline LDL estimates and maxLCBI_4mm (p > 0.05). Patients with maxLCBI4mm > 400 had a significantly increased risk of non-culprit MACE over 2 years with a hazard ratio of 1.67 (1·02–2.74, p = 0.043), with no interaction with LDL estimate groups. The prognostic value of maxLCBI_4mm > 400 also persisted independently of LDL-C trajectory.

Conclusion

Novel LDL estimates have a role in cardiovascular risk assessment but no association with lipid-rich plaque burden indices. Regardless of LDL-C or eLDL-TG, maxLCBI_4mm predicts non-culprit events, capturing a broader spectrum of residual risk than LDL measures alone.

背景和目的NIRS-IVUS （maxLCBI4mm > 400）测量的冠状动脉脂质负荷可预测非罪魁祸首主要不良心脏事件（MACE），但与传统的低密度脂蛋白（LDL）测量结果相关性较弱。我们得出了新的ldl -胆固醇（LDL-C）和ldl -甘油三酯（eLDL-TG）估计值，并评估了它们与maxLCBI4mm的关系。方法在富脂斑块研究（2014-2016）中，采用美国国立卫生研究院（National Institutes of Health）的方程估计参与者的LDL-C和eLDL-TG，并通过独立的Core实验室量化冠状动脉段maxLCBI4mm。采用校正了可能混杂因素的线性回归模型来评估LDL估定值与maxLCBI4mm之间的关系。Kaplan-Meier曲线以maxLCBI4mm≤400 vs. >；400评估非罪魁祸首MACE率，并按LDL-C（≥/<70 mg/dL）和ldl - tg（≥/<；60百分位）分层。Cox比例风险模型以maxLCBI4mm评估非元凶MACE的风险及LDL估计组的效果。结果在626例可评估患者中（410例maxLCBI4mm≤400,216例maxLCBI4mm≤400），基线LDL估值与maxLCBI4mm之间无相关性（p > 0.05）。maxLCBI4mm >； 400患者2年内发生非罪魁祸首MACE的风险显著增加，风险比为1.67 (1.02 - 2.74,p = 0.043)，与LDL估计组无交互作用。maxLCBI4mm >； 400的预后价值也独立于LDL-C轨迹而持续存在。结论新型LDL在心血管风险评估中有一定作用，但与富脂斑块负荷指数无相关性。无论LDL- c还是eLDL-TG， maxLCBI4mm预测非罪魁祸首事件，比单独测量LDL捕获更广泛的剩余风险。

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引用次数: 0

Antisense oligonucleotide inhibition of HMGB1 attenuates angiotensin II-induced abdominal aortic aneurysms 反义寡核苷酸抑制HMGB1减轻血管紧张素ii诱导的腹主动脉瘤

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2025-10-03 DOI: 10.1016/j.atherosclerosis.2025.120527

Shayan Mohammadmoradi , Hisashi Sawada , Sohei Ito , Michael K. Franklin , Deborah A. Howatt , Adam E. Mullick , Hong S. Lu , Alan Daugherty

Background and aims

Vascular inflammation is a hallmark of abdominal aortic aneurysms (AAA) but the mechanism of these effects is undefined. High-mobility group box 1 (HMGB1) has potent inflammatory properties and has been implicated in various vascular diseases. We determined a role for HMGB1 in AAA pathogenesis utilizing an antisense oligonucleotide (ASO) to inhibit synthesis of the protein.

Methods and results

To identify molecular signatures and biological pathways associated with AAA, we analyzed RNA sequencing (RNA-seq) data from patients with AAA (GSE57691) and mice with angiotensin II (AngII)-induced AAA (GSE17901) obtained from the GEO database. Transcriptomic analysis revealed a marked upregulation of HMGB1 in both human and mouse aneurysmal tissue. AngII infusion into male LDLR−/− mice significantly increased HMGB1 protein abundance in the abdominal aorta after 7 days consistent with a role in AAA initiation. To assess the functional role of HMGB1 in AAA formation protein synthesis was inhibited using an ASO. Hypercholesterolemia was induced in male mice by expressing PCSK9-D377Y and maintained on a Western diet before being infused with AngII (1000 ng/kg/min) for 4 weeks to induce AAA. Mice (n = 15 per group) received subcutaneous injections of either phosphate-buffered saline or HMGB1 ASO (25 mg/kg/day) on days 0 and 3, followed by weekly injections for the remainder of the study. HMGB1 ASO administration significantly attenuated AngII-induced AAA formation in the absence of any changes in blood pressure.

Conclusions

ASO-driven HMGB1 inhibition resulted in a profound attenuation of AngII-induced AAA, highlighting its potential as a therapeutic target for AAAs.

背景和目的血管炎症是腹主动脉瘤（AAA）的一个特征，但其机制尚不明确。高迁移率组框1 （HMGB1）具有强大的炎症特性，并与多种血管疾病有关。我们利用反义寡核苷酸（ASO）抑制该蛋白的合成，确定了HMGB1在AAA发病机制中的作用。方法和结果为了确定AAA相关的分子特征和生物学途径，我们分析了从GEO数据库中获得的AAA患者（GSE57691）和血管紧张素II （AngII）诱导的AAA小鼠（GSE17901）的RNA测序（RNA-seq）数据。转录组学分析显示HMGB1在人和小鼠动脉瘤组织中均显著上调。AngII输注雄性LDLR - / -小鼠7天后显著增加腹主动脉HMGB1蛋白丰度，与AAA起始的作用一致。用ASO抑制HMGB1在AAA形成蛋白合成中的功能作用。通过表达PCSK9-D377Y在雄性小鼠中诱导高胆固醇血症，并在西方饮食中维持，然后注入AngII (1000 ng/kg/min) 4周以诱导AAA。小鼠（n = 15 /组）在第0天和第3天皮下注射磷酸盐缓冲盐水或HMGB1 ASO （25 mg/kg/天），然后在研究的其余时间每周注射一次。HMGB1 ASO在没有血压变化的情况下显著减弱血管诱导的AAA形成。结论saso驱动的HMGB1抑制可导致血管损伤诱导的AAA的严重衰减，突出了其作为AAA治疗靶点的潜力。

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引用次数: 0

Single-cell RNA-sequencing reveals adventitial fibroblast alterations during mouse atherosclerosis 单细胞rna测序揭示小鼠动脉粥样硬化过程中内皮成纤维细胞的改变。

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2025-10-03 DOI: 10.1016/j.atherosclerosis.2025.120526

Lauren E. Fries, Allen Chung, Hyun-Kyung Chang, Timothy L. Yuan, Robert C. Bauer

Background

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality in the western world despite the success of lipid lowering therapies, highlighting the need for novel lipid-independent therapeutic strategies. Genome-wide association studies (GWAS) have identified numerous genes associated with ASCVD that function in the vessel wall, suggesting that vascular cells mediate ASCVD, and that the genes and pathways essential for this vascular cell function may be novel therapeutic targets for the treatment of ASCVD. Furthermore, some of these implicated genes appear to function in the adventitial layer of the vasculature, suggesting these cells are able to potentiate ASCVD.

Methods

To investigate the role of adventitial cells in atherosclerosis, we conducted single-cell RNA sequencing (scRNA-seq) of the aortic adventitia during atherogenesis in male Ldlr^−/− mice via pools of three mice, two samples per condition. We cross-referenced the scRNA-seq data with human ASCVD GWAS to identify regulators of adventitial responses in ASCVD. These regulators were then validated in vitro in human adventitial fibroblasts.

Results

We identified four adventitial fibroblast populations, all of which displayed shifts in population size and gene expression over the course of atherogenesis. SERPINH1, an ASCVD-linked GWAS gene, was differentially expressed in adventitial fibroblasts during atherogenesis. Knockdown of SERPINH1 in vitro reduced fibroblast migration and altered subcluster marker gene expression.

Conclusions

These findings reveal dynamic changes in adventitial fibroblasts during atherosclerosis and suggest that reduced SERPINH1 expression disrupts adventitial fibroblast function, contributing to ASCVD progression.

背景：尽管降脂疗法取得了成功，但在西方世界，动脉粥样硬化性心血管疾病（ASCVD）仍然是导致死亡的主要原因，这凸显了对新型非脂类治疗策略的需求。全基因组关联研究（GWAS）已经确定了许多与ASCVD相关的基因，这些基因在血管壁上起作用，这表明血管细胞介导ASCVD，并且这种血管细胞功能所必需的基因和途径可能是治疗ASCVD的新靶点。此外，其中一些相关基因似乎在脉管系统的外皮层中起作用，表明这些细胞能够增强ASCVD。方法：为了研究外膜细胞在动脉粥样硬化中的作用，我们对雄性Ldlr-/-小鼠动脉粥样硬化过程中的主动脉外膜进行了单细胞RNA测序（scRNA-seq），每组3只小鼠，每组2只。我们将scRNA-seq数据与人类ASCVD GWAS交叉引用，以确定ASCVD中非特异性反应的调节因子。这些调节因子随后在体外的人表皮成纤维细胞中得到验证。结果：我们确定了四种外层成纤维细胞群体，它们在动脉粥样硬化过程中都表现出群体大小和基因表达的变化。SERPINH1是一种与ascvd相关的GWAS基因，在动脉粥样硬化过程中，在内皮成纤维细胞中有差异表达。在体外敲低SERPINH1可减少成纤维细胞的迁移并改变亚簇标记基因的表达。结论：这些发现揭示了动脉粥样硬化期间外膜成纤维细胞的动态变化，并提示SERPINH1表达的降低破坏了外膜成纤维细胞的功能，促进了ASCVD的进展。

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引用次数: 0

Association between cardiovascular-kidney-metabolic syndrome, inflammatory biomarkers, and cardiovascular outcomes: Insights from the MESA study 心血管-肾脏代谢综合征、炎症生物标志物和心血管预后之间的关联：来自MESA研究的见解

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2025-10-02 DOI: 10.1016/j.atherosclerosis.2025.120521

Muhammad Imtiaz Ahmad , Parag Chevli , Saeid Mirzai , Jared A. Spitz , Garima Sharma , Joao Lima , Khurram Nasir , Michael J. Blaha , Neha J. Pagidipati , Roger S. Blumenthal , Michael D. Shapiro

Background

This study investigated the association between cardiovascular-kidney-metabolic (CKM) syndrome stages 0–3 and atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF), as well as whether this association varies by interleukin-6 and high-sensitivity C-reactive protein (hsCRP).

Methods

6579 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) were included. Restricted mean survival time (RMST) differences in ASCVD and HF-free survival by CKM syndrome stage, stratified by inflammatory markers, were estimated.

Results

Over a median follow-up of 17.5 years (IQR: 10.5–18.4 years), participants with CKM stage 3 demonstrated significantly shorter ASCVD-free survival compared to stage 0 (−1.94 years; 95 % CI: −2.27, −1.61). Subgroup analysis by IL-6 levels demonstrated differential RMST across CKM stages, with participants having above-median IL-6 levels showing greater survival reduction (−2.5 years; 95 % CI: −3.50, −1.85) than those with below-median levels (−1.46 years; 95 % CI: −1.84, −1.07) (interaction p = 0.002). For heart failure outcomes, categorization by IL-6 levels displayed similar patterns by CKM stage (interaction p = 0.006). Among participants with elevated IL-6, both CKM stages 2 and 3 were associated with reduced HF-free survival (−0.40 years [95 % CI: −0.69, −0.01], and −0.87 years [95 % CI: −1.18, −0.55], respectively). Conversely, participants with lower IL-6 levels showed a significant reduction in HF-free survival only at the CKM stage 3 level (−0.36 years: 95 % CI: −0.57, −0.14). hsCRP stratification yielded comparable results but without significant interactions for either cardiovascular outcome.

Conclusions

These findings suggest that systemic inflammation, as measured by IL-6, may modify the risk of ASCVD and HF associated with CKM syndrome. Therefore, IL-6 measurement could potentially refine risk stratification and prognosis of CKM syndrome stages. However, further studies are needed to assess the clinical relevance of this approach.

背景：本研究探讨了心血管-肾代谢（CKM）综合征0-3期与动脉粥样硬化性心血管疾病（ASCVD）和心力衰竭（HF）之间的关系，以及这种关系是否因白细胞介素-6和高敏c反应蛋白（hsCRP）而异。方法：从多民族动脉粥样硬化研究（MESA）中纳入6579名参与者。通过炎症标记物分层，估计CKM综合征分期ASCVD和无hf生存期的限制平均生存时间（RMST）差异。结果：中位随访17.5年（IQR: 10.5-18.4年），CKM 3期患者的无ascvd生存期明显短于0期患者（-1.94年；95% CI: -2.27, -1.61）。IL-6水平的亚组分析显示了不同CKM分期的RMST差异，IL-6水平高于中位水平的参与者比低于中位水平的参与者（-1.46年，95% CI: -1.84, -1.07）显示出更大的生存减少（-2.5年，95% CI: -3.50, -1.85）（相互作用p = 0.002）。对于心力衰竭的结果，IL-6水平的分类与CKM分期相似（相互作用p = 0.006）。在IL-6升高的参与者中，CKM 2期和3期均与减少的无hf生存相关（分别为-0.40年[95% CI: -0.69, -0.01]和-0.87年[95% CI: -1.18, -0.55]）。相反，IL-6水平较低的参与者仅在CKM 3期水平上显示无hf生存显著减少（-0.36年：95% CI: -0.57, -0.14）。hsCRP分层产生了类似的结果，但对两种心血管结果没有显著的相互作用。结论：这些发现表明，通过IL-6测量的全身性炎症可能会改变与CKM综合征相关的ASCVD和HF的风险。因此，检测IL-6有可能改善CKM综合征分期的风险分层和预后。然而，需要进一步的研究来评估这种方法的临床相关性。

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引用次数: 0

Influenza vaccination and cardiovascular protection: cardiologists need guidance, not only guidelines 流感疫苗接种和心血管保护：心脏病专家需要指导，而不仅仅是指南。

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2025-10-01 DOI: 10.1016/j.atherosclerosis.2025.120483

Nicolas Dauby

引用次数: 0

Lp(a) testing for the primary prevention of cardiovascular disease in high-income countries: a cost-effectiveness analysis 高收入国家心血管疾病一级预防的Lp(a)检测：成本效益分析。

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2025-10-01 DOI: 10.1016/j.atherosclerosis.2025.120447

Jedidiah I. Morton , Florian Kronenberg , Magdalena Daccord , Nicola Bedlington , Marius Geanta , Tobias Silberzahn , Zhenyue Chen , Jean-Luc Eisele , Bogi Eliasen , Mariko Harada-Shiba , Marc Rijken , Albert Wiegman , George Thanassoulis , Pia R. Kamstrup , Iñaki Gutierrez-Ibarluzea , Pablo Coral , Raul D. Santos , Erik Stroes , Michal Vrablik , Gerald F. Watts , Zanfina Ademi

Background and aims

Cost-effectiveness of Lipoprotein(a) [Lp(a)] testing is not established. We aimed to evaluate the cost-effectiveness of Lp(a) testing in the cardiovascular disease (CVD) primary prevention population from healthcare and societal perspectives.

Methods

We constructed and validated a multi-state microsimulation Markov model for a population of 10,000 individuals aged between 40 and 69 years without CVD, selected randomly from the UK Biobank. The model evaluated Lp(a) testing in individuals not initially classified as high-risk based on age, diabetes status, or the SCORE-2 algorithm. Those with an Lp(a) level ≥105 nmol/L (50 mg/dL) were treated as high risk (initiation of a statin plus blood pressure lowering). The Lp(a) testing intervention was compared to standard of care. The primary analyses were conducted from the Australian and UK healthcare perspectives in 2023AUD/GBP. A cost adaptation method estimated cost-effectiveness in multiple European countries, Canada, and the USA.

Results

Among 10,000 individuals, 1,807 had their treatment modified from Lp(a) testing. This led to 217 and 255 quality-adjusted life years gained in Australia and the UK, respectively, with corresponding incremental cost-effectiveness ratios of 12,134 (cost-effective) and −3,491 (cost-saving). From a societal perspective, Lp(a) testing saved $85 and £263 per person in Australia and the UK, respectively. Lp(a) testing was cost-saving among all countries tested in the cost adaptation analysis.

Conclusions

Lp(a) testing in the primary prevention population to reclassify CVD risk and treatment is cost-saving and warranted to prevent CVD.

背景和目的：脂蛋白(a) [Lp(a)]检测的成本效益尚未确定。我们旨在从医疗保健和社会角度评估Lp(a)检测在心血管疾病（CVD）一级预防人群中的成本效益。方法：我们构建并验证了一个多状态微观模拟马尔可夫模型，该模型适用于从英国生物银行随机选择的10,000名年龄在40至69岁之间无心血管疾病的个体。该模型评估了最初根据年龄、糖尿病状况或SCORE-2算法未被分类为高风险的个体的Lp(a)检测。Lp(a)水平≥105 nmol/L （50 mg/dL）的患者被视为高风险（开始使用他汀类药物并降低血压）。将Lp(a)测试干预与标准护理进行比较。主要分析是从2023澳元/英镑的澳大利亚和英国医疗保健角度进行的。一种成本调整方法估算了多个欧洲国家、加拿大和美国的成本效益。结果：在10,000个人中，1,807人的治疗方法从Lp(a)测试中修改。这导致澳大利亚和英国分别增加了217年和255年的质量调整寿命，相应的增量成本效益比为12,134（成本效益）和-3,491（成本节约）。从社会角度来看，在澳大利亚和英国，Lp(a)检测分别为每人节省了85美元和263英镑。在成本适应分析中，Lp(a)检测在所有接受测试的国家中都节省了成本。结论：在一级预防人群中进行Lp(a)检测以重新划分CVD风险和治疗是节省成本的，并且有必要预防CVD。

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引用次数: 0