香烟焦油通过CAMKII/Drp1/mtDNA促进ECs热亡

IF 8.4 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC: Basic to Translational Science Pub Date : 2025-08-01 DOI:10.1016/j.jacbts.2025.03.015

Xing Luo PhD , Ji Li PhD , Yuwu Chen MD , Xiuzhu Weng MD , Xiaoyi Bao PhD , Xiaoxuan Bai MD , Ying Lv PhD , Shan Zhang PhD , Xinxin Zhu MD , Biyi Xu MD , Chen Zhao MD , Ming Zeng MD , Tianyu Wu MD , Qianhui Sun MD , Shengfang Wang PhD , Minghao Liu MD , Thomas Johnson PhD , Stephen J. White PhD , Peter Libby MD , Sining Hu PhD , Haibo Jia PhD

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引用次数: 0

摘要

吸烟是导致斑块侵蚀的唯一心血管风险因素。我们发现香烟焦油导致载脂蛋白E - / -小鼠的侵蚀样病变发展，伴有壁血栓形成、内皮不连续、血小板活化、平滑肌细胞增殖和主动脉透明质酸积累。单细胞转录组学显示，内皮细胞亚群中与焦亡、血小板活化和白细胞粘附相关的基因显著增加。救援试验表明，卷烟焦油通过激活Ca2+信号通路，增强钙钙调素依赖性蛋白激酶II /动力蛋白相关蛋白1介导的线粒体分裂和线粒体DNA释放，导致人冠状动脉内皮细胞焦亡。抑制内皮细胞焦亡可能是一种新的治疗策略，以减少斑块侵蚀。

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Cigarette Tar Enhanced ECs Pyroptosis via CAMKII/Drp1/mtDNA

Smoking is the only cardiovascular risk factor for plaque erosion. We found cigarette tar resulted in erosion-like lesion development in apolipoprotein E^−/− mice, with mural thrombosis, discontinuous endothelium, platelet activation, smooth muscle cell proliferation, and hyaluronic acid accumulation in the aorta. Single-cell transcriptomics revealed that genes relating to pyroptosis, platelet activation, and leukocytes adhesion were significantly increased in an endothelial cell subset. Rescue assays indicated cigarette tar caused human coronary artery endothelial cell pyroptosis by enhanced calcium–calmodulin-dependent protein kinase II / dynamin-related protein 1–mediated mitochondrial fission and mitochondrial DNA release via activating Ca²⁺ signaling. Inhibition of endothelial cell pyroptosis may be a novel therapeutic strategy to reduce plaque erosion.

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来源期刊

JACC: Basic to Translational Science CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

14.20

自引率

1.00%

发文量

161

审稿时长

16 weeks

期刊介绍： JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.