HSPB1 Regulates Autophagy and Apoptosis in Vascular Smooth Muscle Cells in Arteriosclerosis Obliterans.

IF 3.4 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Therapeutics Pub Date : 2022-01-01 DOI:10.1155/2022/3889419

Keqin Chen, Changmiao Hou, Lei Xu, Hanwu Peng, Chaogui He, Jing Liu, Guoqing Wang, Shaoshuai Huang, Xiehong Liu

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引用次数: 1

Abstract

Objective: Small heat shock protein-1 (HSPB1) is a small heat shock protein that participates in many cellular processes and alleviates stress-induced cell injury. Autophagy protects cells from many types of stress and plays a key role in preventing stress in arteriosclerosis obliterans (ASO). However, the roles of HSPB1 in autophagy and apoptosis in the context of ASO pathogenesis remain unclear.

Methods: In vivo and in vitro studies were used to determine whether HSPB1 is associated with ASO progression. The expression of HSPB1 was measured in normal and sclerotic blood vessels. The role of HSPB1 and its potential downstream signaling pathway were determined in VSMCs by overexpressing and silencing HSPB1.

Results: A total of 91 ASO patients admitted to and treated at our hospital from Sep. 2020 to Sep. 2021 were selected, and plasma HSPB1 expression was assessed. We divided the patients with ASO into the grade I (n = 39), II (n = 29), III (n = 10), and IV (n = 13) groups according to Fontaine's classification. Plasma HSPB1 levels were markedly decreased in patients with grade III (n = 10) and IV (n = 13) ASO compared with patients with grade I ASO. Furthermore, HSPB1 expression was significantly decreased, and p62 and cleaved caspase-3 were increased in the sclerotic vasculature compared to the normal vasculature (p < 0.05). Overexpression of HSPB1 promoted apoptosis of VSMCs following ox-LDL treatment. Knockdown of HSPB1 led to a marked increase in the expression of LC3II and Beclin-1 in ox-LDL-stimulated VSMCs, whereas knockdown of HSPB1 attenuated these changes (p < 0.05). Importantly, overexpression of HSPB1 promoted the dephosphorylation of JNK in ox-LDL-stimulated VSMCs. Conversely, downregulation of HSPB1 induced the opposite change.

Conclusion: Loss of HSPB1 promotes VSMC autophagy and inhibits VSMC apoptosis, which are associated with ASO. HSPB1 and its downstream signaling pathways could be potential therapeutic targets for ASO treatment.

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HSPB1调控闭塞动脉硬化血管平滑肌细胞的自噬和凋亡。

目的:小热休克蛋白-1 (HSPB1)是一种小热休克蛋白，参与许多细胞过程，减轻应激诱导的细胞损伤。自噬保护细胞免受多种应激，并在动脉硬化闭塞症(ASO)的应激预防中起关键作用。然而，在ASO发病机制中，HSPB1在自噬和凋亡中的作用尚不清楚。方法:采用体内和体外研究确定HSPB1是否与ASO进展相关。检测HSPB1在正常和硬化血管中的表达。通过过表达和沉默HSPB1，确定了HSPB1在vsmc中的作用及其潜在的下游信号通路。结果:选取我院2020年9月至2021年9月收治的ASO患者91例，评估其血浆HSPB1表达水平。我们根据Fontaine的分类将ASO患者分为I级(n = 39)、II级(n = 29)、III级(n = 10)和IV级(n = 13)组。与I级ASO患者相比，III级(n = 10)和IV级(n = 13) ASO患者血浆HSPB1水平明显降低。此外，与正常血管相比，硬化血管中HSPB1表达显著降低，p62和cleaved caspase-3表达升高(p < 0.05)。HSPB1过表达促进ox-LDL处理后VSMCs的凋亡。敲低HSPB1导致ox- ldl刺激的VSMCs中LC3II和Beclin-1的表达显著增加，而敲低HSPB1则使这些变化减弱(p < 0.05)。重要的是，在ox- ldl刺激的VSMCs中，HSPB1的过表达促进了JNK的去磷酸化。相反，HSPB1的下调会引起相反的变化。结论:HSPB1缺失促进VSMC自噬，抑制VSMC凋亡，与ASO有关。HSPB1及其下游信号通路可能是ASO治疗的潜在靶点。

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

Cardiovascular Therapeutics 医学-心血管系统

CiteScore

5.60

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： Cardiovascular Therapeutics (formerly Cardiovascular Drug Reviews) is a peer-reviewed, Open Access journal that publishes original research and review articles focusing on cardiovascular and clinical pharmacology, as well as clinical trials of new cardiovascular therapies. Articles on translational research, pharmacogenomics and personalized medicine, device, gene and cell therapies, and pharmacoepidemiology are also encouraged. Subject areas include (but are by no means limited to): Acute coronary syndrome Arrhythmias Atherosclerosis Basic cardiac electrophysiology Cardiac catheterization Cardiac remodeling Coagulation and thrombosis Diabetic cardiovascular disease Heart failure (systolic HF, HFrEF, diastolic HF, HFpEF) Hyperlipidemia Hypertension Ischemic heart disease Vascular biology Ventricular assist devices Molecular cardio-biology Myocardial regeneration Lipoprotein metabolism Radial artery access Percutaneous coronary intervention Transcatheter aortic and mitral valve replacement.