Meteorin-like (METRNL) attenuates hypertensive induced cardiac hypertrophy by inhibiting autophagy via activating BRCA2

Biochim Biophys Acta Mol Basis Dis. 2024 Apr;1870(4):167113. doi: 10.1016/j.bbadis.2024.167113. Epub 2024 Mar 7.

Abstract

Hypertension, a prevalent cardiovascular ailment globally, can precipitate numerous complications, notably hypertensive cardiomyopathy. Meteorin-like (METRNL) is demonstrated to possess potential protective properties on cardiovascular diseases. However, its specific role and underlying mechanism in hypertensive myocardial hypertrophy remain elusive. Spontaneously hypertensive rats (SHRs) served as hypertensive models to explore the effects of METRNL on hypertension and its induced myocardial hypertrophy. The research results indicate that, in contrast to Wistar-Kyoto (WKY) rats, SHRs exhibit significant symptoms of hypertension and myocardial hypertrophy, but cardiac-specific overexpression (OE) of METRNL can partially ameliorate these symptoms. In H9c2 cardiomyocytes, METRNL suppresses Ang II-induced autophagy by controlling the BRCA2/Akt/mTOR signaling pathway. But when BRCA2 expression is knocked down, this effect will be suppressed. Collectively, METRNL emerges as a potential therapeutic target for hypertensive cardiomyopathy.

Keywords: Autophagy; Breast cancer susceptibility gene 2 (BRCA2); Cardiac hypertrophy; Hypertension; METRNL.

MeSH terms

  • Animals
  • Autophagy / genetics
  • Cardiomegaly / drug therapy
  • Cardiomegaly / genetics
  • Cardiomyopathies* / metabolism
  • Hypertension* / complications
  • Hypertension* / drug therapy
  • Hypertension* / genetics
  • Myocytes, Cardiac / metabolism
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY