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Research Paper|Volume 14, Issue 6|pp 2548—2557

Maslinic acid protects against pressure-overload-induced cardiac hypertrophy by blocking METTL3-mediated m6A methylation

Ming Fang1, Jun Deng1, Qiangping Zhou1, Zhengbang Hu1, Lixia Yang2
  • 1Department of Emergency, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
  • 2Department of Infectious Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
Received: May 4, 2021Accepted: December 10, 2021Published: March 28, 2022
https://doi.org/10.18632/aging.203860

≈ Copyright: © 2022 Fang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Coordinated response of the heart to physiological stressors (including stress overload, ischemia, hypothyroidism, and metabolic signals) is a hallmark of heart disease. However, effective treatment and its molecular targets are unknown. Although Maslinic Acid (MA) has been shown to inhibit inflammatory responses with strong anti-tumor, anti-bacterial, and antioxidant effects, information on its role and underlying mechanism in cardiac hypertrophy are scanty. The present study revealed that 10-103 μg/ml MA treatment significantly inhibited Ang-II induced hypertrophy in NMCMs and the dosage did not influence the cell viability of H9C2 and NCMCs. Moreover, the anti-hypertrophy effect of MA (30 mg/kg·day) was verified in the TAC-induced hypertrophy mouse model in vivo. Further analysis showed that MA administration decreased the total RNA m6A methylation and METTL3 levels in Ang-II treated NMCMs and TAC stressed hearts. Rescue experiments under adenovirus-mediated myocardial METTL3 overexpression confirmed that METTL3-mediated m6A methylation is essential in M-driven inhibition of myocardial hypertrophy. Collectively, MA exerts a significant anti-hypertrophy effect by regulating the modification of METTL3-mediated m6A methylation in vitro and in vivo. These findings may provide a platform for establishing a new target and strategy for cardiac hypertrophy treatment.