TRPC5-mediated NLRP3 inflammasome activation contributes to myocardial cell pyroptosis in chronic intermittent hypoxia rats.

IF 2.1 4区医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS Acta cardiologica Pub Date : 2024-09-01 Epub Date: 2024-10-08 DOI:10.1080/00015385.2024.2408137

Yu Li, Sharezhati Yishajiang, Yulan Chen, Gulinazi Tulahong, Wen Wen, Mengmeng Wang, Zhiqiang Li

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Abstract

Background: Chronic intermittent hypoxia (CIH) is the primary cause of myocardial inflammation in obstructive sleep apnea-hypopnea syndrome (OSAHS). Pyroptosis is a newly discovered form of programmed cell death accompanying inflammatory reactions. Our previous study showed that TRPC5 is upregulated in the myocardial injury of CIH rats. The present study aimed to explore the role of TRPC5 in CIH-induced myocardial cell pyroptosis.

Methods: A model of CIH in OSA rats was established. SD rats were randomly divided into control group(8rats) and OSA group(8rats). Scanning electron microscope(SEM) was performed on left ventricular tissues slides. Western blot were used to detect the expression levels of pyroptosis-related factors and TRPC5 and its downstream proteins in myocardia tissue.

Results: The pyroptosis of myocardial cells by SEM revealed damaged cell membrane integrity of OSA group rats, with fibrous tissue attached to the cell membrane surface, and vesicular protrusions and pyroptotic bodies were observed. Compared to the control group, the expression of pyroptosis-related proteins, such as caspase1, pro-IL-1β, IL-1β, IL-18, GSDMD, and GSDMD-N was upregulated in the OSA group (p < 0.05). Compared to the control group, the expression of TRPC5, NLPR3, p-CaMKIIβ + δ+γ, and HDAC4 was higher in the OSA group (p < 0.05).

Conclusions: These findings indicated that the pyroptosis response increases in CIH-induced myocardial injury, and the mechanism that TRPC5 is upregulated, promoting the expression of NLRP3 and inflammasome formation through CaMKII phosphorylation and HDAC4 cytoplasmic translocation. This might be a potential target for the treatment of OSA-induced myocardial injury.

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TRPC5介导的NLRP3炎症小体活化导致慢性间歇性缺氧大鼠心肌细胞脓毒症。

背景：慢性间歇性缺氧（CIH）是阻塞性睡眠呼吸暂停-低通气综合征（OSAHS）心肌炎症的主要原因。嗜热细胞增多症是一种新发现的伴随炎症反应的程序性细胞死亡形式。我们之前的研究表明，TRPC5 在 CIH 大鼠心肌损伤中上调。本研究旨在探讨 TRPC5 在 CIH 诱导的心肌细胞猝死中的作用：方法：建立 OSA 大鼠 CIH 模型。方法：建立 OSA 大鼠 CIH 模型，将 SD 大鼠随机分为对照组（8 只）和 OSA 组（8 只）。用扫描电子显微镜（SEM）观察左心室组织切片。用Western blot检测心肌组织中热休克相关因子和TRPC5及其下游蛋白的表达水平：与对照组相比，OSA 组心肌细胞热解相关蛋白如 caspase1、pro-IL-1β、IL-1β、IL-18、GSDMD 和 GSDMD-N 的表达上调（p p 结论）：这些研究结果表明，CIH 诱导的心肌损伤中热休克反应增加，其机制是 TRPC5 上调，通过 CaMKII 磷酸化和 HDAC4 胞质转位促进 NLRP3 的表达和炎性体的形成。这可能是治疗 OSA 诱导的心肌损伤的潜在靶点。

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来源期刊

Acta cardiologica 医学-心血管系统

CiteScore

2.50

自引率

12.50%

发文量

115

审稿时长

2 months

期刊介绍： Acta Cardiologica is an international journal. It publishes bi-monthly original, peer-reviewed articles on all aspects of cardiovascular disease including observational studies, clinical trials, experimental investigations with clear clinical relevance and tutorials.