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

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 ( < 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).

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.