PRMT5 up-regulation improves myocardial hypertrophy by mediating E2F-1/NF-KB/NLRP3 pathway

Various protein arginine methyltransferases (PRMTs) have been demonstrated to be aberrantly expressed in cardiovascular disease. This study aimed to investigate the role of PRMT5 in myocardial hypertrophy. Levels of fibrosis markers, NLRP3-ASC-Caspase1, inflammatory factors, myocardial hypertrophy markers and oxidative stress markers were determined in cardiomyocytes. Overexpression or knockdown models of PRMT5 and E2F-1 were constructed, and pharmacological intervention with NF -KB was determine the function of the PRMT5/E2F-1/NF-KB pathway in myocardial hypertrophy. Results shows that PRMT5 was down-regulated in the TAC rat model as well as in an in-vitro model of Ang II-induced myocardial hypertrophy. Overexpression of PRMT5 dramatically reduced Ang II-induced myocardial hypertrophy, fibrosis, inflammatory response, and oxidative stress, whereas knockdown of PRMT5 had the opposite effect. PRMT5 overexpression restrained E2F-1 expres-sion and impaired NF -KB phosphorylation and NLRP3-ASC-Caspase1 inflammasome activation. Mechanistically, PRMT5 knockdown contributed to E2F-1 expression, but E2F-1 knockdown or NF -KB inhibition reversed PRMT5 knockdown-mediated myocardial hypertrophy. PRMT5 attenuated NLRP3 inflammasome activation and ame-liorates angiotensin II-induced myocardial hypertrophy by regulating the E2F-1/NF-KB pathway.

Automated summary

This study investigated the role of PRMT5 in myocardial hypertrophy and found that overexpression of PRMT5 could reduce myocardial hypertrophy, fibrosis, inflammation, and oxidative stress. Knockdown of PRMT5 had the opposite effect. PRMT5 regulated the activation of NLRP3 inflammasome by modulating the E2F-1/NF-KB pathway, thereby attenuating myocardial hypertrophy.