Second Department of General Internal Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Department of Hypertension, The People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China.
Acta Cardiol. 2024 Sep;79(7):796-804. doi: 10.1080/00015385.2024.2408137. Epub 2024 Oct 8.
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.
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.
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 ( < 0.05). Compared to the control group, the expression of TRPC5, NLPR3, p-CaMKIIβ + δ+γ, and HDAC4 was higher in the OSA group ( < 0.05).
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.
慢性间歇性低氧（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。细胞焦亡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 诱导的心肌细胞细胞焦亡中的作用。
建立 OSA 大鼠 CIH 模型。SD 大鼠随机分为对照组（8 只）和 OSA 组（8 只）。对左心室组织切片进行扫描电子显微镜（SEM）检查。Western blot 用于检测心肌组织中细胞焦亡相关因子和 TRPC5 及其下游蛋白的表达水平。
SEM 显示 OSA 组大鼠心肌细胞发生细胞焦亡，细胞膜完整性受损，细胞膜表面附有纤维组织，观察到小泡突起和细胞焦亡小体。与对照组相比，OSA 组细胞焦亡相关蛋白如 caspase1、pro-IL-1β、IL-1β、IL-18、GSDMD 和 GSDMD-N 的表达上调（ < 0.05）。与对照组相比，OSA 组 TRPC5、NLPR3、p-CaMKIIβ + δ+γ 和 HDAC4 的表达更高（ < 0.05）。
这些发现表明，CIH 诱导的心肌损伤中细胞焦亡反应增加，TRPC5 上调的机制是通过 CaMKII 磷酸化和 HDAC4 细胞质易位促进 NLRP3 表达和炎性小体形成。这可能是治疗 OSA 引起的心肌损伤的潜在靶点。
