Prmt7 regulates the JAK/STAT/Socs3 signaling pathway in postmenopausal cardiomyopathy

Abstract

Protein arginine methyltransferases (PRMTs) modulate diverse cellular processes, including stress responses. The present study explored the role of Prmt7 in protecting against menopause-associated cardiomyopathy. Mice with cardiac-specific Prmt7 ablation (cKO) exhibited sex-specific cardiomyopathy. Male cKO mice exhibited impaired cardiac function, myocardial hypertrophy, and interstitial fibrosis associated with increased oxidative stress. Interestingly, female cKO mice predominantly exhibited comparable phenotypes only after menopause or ovariectomy (OVX). Prmt7 inhibition in cardiomyocytes exacerbated doxorubicin (DOX)-induced oxidative stress and DNA double-strand breaks, along with apoptosis-related protein expression. Treatment with 17β-estradiol (E2) attenuated the DOX-induced decrease in Prmt7 expression in cardiomyocytes, and Prmt7 depletion abrogated the protective effect of E2 against DOX-induced cardiotoxicity. Transcriptome analysis of ovariectomized wild-type (WT) or cKO hearts and mechanical analysis of Prmt7-deficient cardiomyocytes demonstrated that Prmt7 is required for the control of the JAK/STAT signaling pathway by regulating the expression of suppressor of cytokine signaling 3 (Socs3), which is a negative feedback inhibitor of the JAK/STAT signaling pathway. These data indicate that Prmt7 has a sex-specific cardioprotective effect by regulating the JAK/STAT signaling pathway and, ultimately, may be a potential therapeutic tool for heart failure treatment depending on sex.

Prmt7: The New Hope Against Gender-Specific Heart Failure

Heart disease, a major cause of death globally, affects men more than women. However, women after menopause are at greater risk than those before menopause. Scientists have discovered that the sex hormone E2 (a type of estrogen) helps protect against heart disease. In a recent study, a protein named Prmt7 was found to protect heart cells from heart failure. The study, which involved tests on mice and cell cultures (cells grown in a lab), showed that female mice without Prmt7 developed heart issues as they aged. The study also showed that Prmt7 is needed for E2 to fully function in heart cells. This suggests that Prmt7 could be a potential treatment target for heart failure, especially in women after menopause.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.