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

Byeong-Yun Ahn1, Yan Zhang1, Shibo Wei1

  • 1Department of Molecular Cell Biology, Sungkyunkwan University, School of Medicine, Suwon, Republic of Korea.

Experimental & Molecular Medicine
|March 15, 2024
PubMed

Insights

Protein arginine methyltransferase 7 (Prmt7) protects against heart disease in a sex-specific manner. Prmt7 deficiency leads to cardiomyopathy, particularly in males and post-menopausal females, by impacting the JAK/STAT pathway.

Area of Science:

  • Cardiovascular Biology
  • Epigenetics
  • Molecular Medicine

Background:

  • Protein arginine methyltransferases (PRMTs) are crucial regulators of cellular processes, including stress responses.
  • Menopause-associated cardiomyopathy is a significant health concern, particularly in aging populations.
  • The specific role of PRMT7 in cardiac health and its sex-specific regulation remain largely unexplored.

Purpose of the Study:

  • To investigate the role of Protein arginine methyltransferase 7 (Prmt7) in protecting against menopause-associated cardiomyopathy.
  • To elucidate the sex-specific effects of Prmt7 deficiency on cardiac function and structure.
  • To identify the molecular mechanisms underlying Prmt7's cardioprotective actions.

Main Methods:

  • Generation of cardiac-specific Prmt7 knockout (cKO) mice to assess cardiac function and pathology.
  • In vitro studies using cardiomyocytes to evaluate the impact of Prmt7 inhibition on oxidative stress and DNA damage.
  • Transcriptome analysis and JAK/STAT signaling pathway evaluation in ovariectomized mice and Prmt7-deficient cardiomyocytes.
  • Assessment of 17β-estradiol (E2) effects on Prmt7 expression and cardiotoxicity.

Main Results:

  • Cardiac-specific Prmt7 ablation (cKO) resulted in sex-specific cardiomyopathy, with male cKO mice showing impaired cardiac function, hypertrophy, and fibrosis.
  • Female cKO mice exhibited comparable phenotypes primarily after menopause or ovariectomy (OVX).
  • Prmt7 inhibition exacerbated doxorubicin (DOX)-induced cardiotoxicity, oxidative stress, and DNA damage in cardiomyocytes.
  • Prmt7 regulates the JAK/STAT signaling pathway by controlling Suppressor of Cytokine Signaling 3 (Socs3) expression.
  • Prmt7 depletion abrogated the protective effects of 17β-estradiol (E2) against DOX-induced cardiotoxicity.

Conclusions:

  • Prmt7 plays a critical sex-specific role in cardioprotection against menopause-associated damage.
  • Prmt7's mechanism involves the regulation of the JAK/STAT signaling pathway via Socs3.
  • Prmt7 emerges as a potential therapeutic target for heart failure, with considerations for sex-specific approaches.

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