促进动脉导线损伤后新生内膜形成的是补体因子 B，而非膜攻击复合物成分 C9

IF 4.9 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis Pub Date : 2024-10-23 DOI:10.1016/j.atherosclerosis.2024.118586

Ziyi Guo , Yuze Zhang , Zekun Peng , Haojie Rao , Jianfeng Yang , Zengrong Chen , Wenchao Song , Qing Wan , Hong Chen , Miao Wang

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引用次数: 0

摘要

背景和目的新内膜增生引起的血管再狭窄限制了支架动脉的长期通畅，导致血管成形术失败。补体系统与血管再狭窄有关。本研究旨在探讨补体激活替代途径的重要组成部分--补体因子 B（fB）在新生内膜形成中的作用。方法使用缺乏 fB 或 C9（膜攻击复合物 C5b-9 的主要成分）的 12 周大小鼠和同窝对照组进行血管成形术线损伤，并评估新生内膜的形成。在体外检测了血管平滑肌细胞（SMC）和内皮细胞（EC）的增殖和迁移。损伤后 28 天，缺失 fB 可显著减少新生内膜面积和内膜与中膜面积比，但不影响中膜面积。损伤后 7 天，缺乏 fB 会减少 SMC 的增殖，但不会改变新生内膜巨噬细胞的浸润和 EC 的再内皮化。血管SMC表达的fB，而非循环来源的fB，在体外SMC增殖和迁移中发挥了重要作用。fB缺乏的小鼠表现出较低水平的可溶性C5b-9，然而，C9的缺失并没有改变钢丝损伤后新内膜的形成，这与C9缺乏对体外SMC增殖的无效影响一致。这归因于 fB 依赖于 SMC 的增殖和迁移，而不影响 EC 的功能。以 fB 为靶点可预防经皮冠状动脉介入治疗后的再狭窄。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Complement factor B, not the membrane attack complex component C9, promotes neointima formation after arterial wire injury

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Complement factor B, not the membrane attack complex component C9, promotes neointima formation after arterial wire injury

Background and aims

Vascular restenosis due to neointima hyperplasia limits the long-term patency of stented arteries, resulting in angioplasty failure. The complement system has been implicated in restenosis. This study aimed to investigate the role of complement factor B (fB), an essential component of the alternative pathway of complement activation, in neointima formation.

Methods

Angioplasty wire injury was conducted using 12-week-old mice deficient in fB or C9 (the main component of the membrane attacking complex, C5b-9) and littermate controls and neointima formation were assessed. Vascular smooth muscle cell (SMC) and endothelial cell (EC) proliferation and migration were examined in vitro.

Results

fB was mainly detected in SMCs of stenotic arteries from humans and mice. Deletion of fB substantially reduced the neointima area and intima-to-media area ratio without affecting the media area at 28 days after injury. At 7 days after injury, fB deficiency decreased SMC proliferation, unaltering neointimal macrophage infiltration and EC reendothelialization. Vascular SMC-expressed fB, not the circulation-sourced fB, played an essential role in SMC proliferation and migration in vitro. fB deficient mice exhibited lower levels of the soluble form of C5b-9, however, deletion of C9 did not alter neointima formation after wire injury, consistent with the null impact of C9 deficiency on SMC proliferation in vitro.

Conclusions

fB promotes neointima formation following wire-induced artery injury independent of forming the membrane-attacking complex. This is attributable to fB-dependent SMC proliferation and migration without affecting EC function. Targeting fB might protect against restenosis after percutaneous coronary intervention.

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来源期刊

Atherosclerosis 医学-外周血管病

CiteScore

9.80

自引率

3.80%

发文量

1269

审稿时长

36 days

期刊介绍： Atherosclerosis has an open access mirror journal Atherosclerosis: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. Atherosclerosis brings together, from all sources, papers concerned with investigation on atherosclerosis, its risk factors and clinical manifestations. Atherosclerosis covers basic and translational, clinical and population research approaches to arterial and vascular biology and disease, as well as their risk factors including: disturbances of lipid and lipoprotein metabolism, diabetes and hypertension, thrombosis, and inflammation. The Editors are interested in original or review papers dealing with the pathogenesis, environmental, genetic and epigenetic basis, diagnosis or treatment of atherosclerosis and related diseases as well as their risk factors.