PCSK9 and coronary atherosclerosis progression beyond LDL-cholesterol in coronary artery disease patients.

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation Pub Date : 2025-06-04 DOI:10.1111/eci.70083

Rosetta Ragusa, Silvia Rocchiccioli, Serena Del Turco, Antonio Morlando, Giuseppina Basta, Arthur Scholte, Danilo Neglia, Chiara Caselli

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引用次数: 0

Abstract

Background: This study evaluated whether plasma PCSK9 is associated with coronary plaque progression in patients with coronary artery disease (CAD) and assessed its involvement in molecular processes of atherogenesis.

Methods: Plasma PCSK9 was measured in 159 patients with stable CAD submitted to coronary computed tomography angiography (CTA) at baseline and after a follow-up of 6.5 ± 1.1 years. Plaque progression was defined as the annual increase in Total, Fibrous, Fibro-fatty, Necrotic-Core and Dense-Calcium plaque volumes (PV). Pathways linked with PCSK9 were studied by RNA-sequencing of whole blood and in vitro studies using endothelial cells (EC).

Results: At multivariable analysis, plasma PCSK9 was associated with an annual increase in Necrotic-Core PV (p = .022) independent of cardiovascular risk factors, molecular markers, and medications, including LDL-C and statins. At RNA-seq analysis, PCSK9 was linked to the expression of genes involved in the innate-immune response. Treating EC with PCSK9 resulted in a significant increase in ICAM-1, VCAM-1, MCP1 and IL6 mRNA expression.

Conclusions: In patients with CAD, plasma PCSK9 is associated with progression of Necrotic Core-PV. The link with inflammatory pathways suggested for PCSK9 a potential role for the occurrence of prognostically adverse plaque phenotypes beyond LDL-C regulation.

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冠心病患者的PCSK9与冠状动脉粥样硬化进展的关系

背景：本研究评估血浆PCSK9是否与冠状动脉疾病（CAD）患者冠状动脉斑块进展相关，并评估其在动脉粥样硬化分子过程中的参与。方法：对159例经冠状动脉ct血管造影（CTA）检查的稳定型CAD患者在基线和随访6.5±1.1年后的血浆PCSK9进行测定。斑块进展被定义为总斑块、纤维斑块、纤维脂肪斑块、坏死核心斑块和致密钙斑块体积（PV）的年度增加。通过全血rna测序和内皮细胞（EC）体外研究，研究了与PCSK9相关的途径。结果：在多变量分析中，血浆PCSK9与坏死性核心PV的年增加相关（p = 0.022），独立于心血管危险因素、分子标志物和药物（包括LDL-C和他汀类药物）。在RNA-seq分析中，PCSK9与先天免疫应答相关基因的表达有关。PCSK9处理EC可显著增加ICAM-1、VCAM-1、MCP1和IL6 mRNA的表达。结论：在冠心病患者中，血浆PCSK9与坏死性核心pv的进展有关。与炎症途径的联系表明PCSK9在LDL-C调节之外的预后不良斑块表型的发生中具有潜在作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Clinical Investigation 医学-医学：内科

CiteScore

9.50

自引率

3.60%

发文量

192

审稿时长

1 months

期刊介绍： EJCI considers any original contribution from the most sophisticated basic molecular sciences to applied clinical and translational research and evidence-based medicine across a broad range of subspecialties. The EJCI publishes reports of high-quality research that pertain to the genetic, molecular, cellular, or physiological basis of human biology and disease, as well as research that addresses prevalence, diagnosis, course, treatment, and prevention of disease. We are primarily interested in studies directly pertinent to humans, but submission of robust in vitro and animal work is also encouraged. Interdisciplinary work and research using innovative methods and combinations of laboratory, clinical, and epidemiological methodologies and techniques is of great interest to the journal. Several categories of manuscripts (for detailed description see below) are considered: editorials, original articles (also including randomized clinical trials, systematic reviews and meta-analyses), reviews (narrative reviews), opinion articles (including debates, perspectives and commentaries); and letters to the Editor.