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

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2024-04, Vol.1870 (4), p.167113, Article 167113
• Main Authors: Li, Jun, Hong, Yinghui, Zhong, Yinsheng, Yang, Shujun, Pei, Liying, Huang, Zijie, Long, Huibao, Chen, Xuxiang, Zhou, Changqing, Zheng, Guanghui, Zeng, Chaotao, Wu, Haidong, Wang, Tong
• Format: Article
• Language: English
• Subjects: Animals; Autophagy; Autophagy - genetics; Breast cancer susceptibility gene 2 (BRCA2); Cardiac hypertrophy; Cardiomegaly - drug therapy; Cardiomegaly - genetics; Cardiomyopathies - metabolism; Hypertension; Hypertension - complications; Hypertension - drug therapy; Hypertension - genetics; METRNL; Myocytes, Cardiac - metabolism; Rats; Rats, Inbred SHR; Rats, Inbred WKY
• ISSN: 0925-4439; 1879-260X; 1879-260X
• DOI: 10.1016/j.bbadis.2024.167113

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. [Display omitted] •METRNL expression decreases in cardiac tissues of spontaneously hypertensive rats (SHRs).•METRNL overexpression can alleviate hypertension and pathological cardiac hypertrophy in SHRs.•METRNL inhibits excessive autophagy in both SHRs cardiac tissue and AngII-induced H9c2 cardiomyocytes.•METRNL can alleviate hypertensive cardiac hypertrophy via inhibiting excessive autophagy by activating BRCA2/Akt/mTOR signaling.