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Updated: Jul 4, 2026
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Technique of Minimally Invasive Transverse Aortic Constriction in Mice for Induction of Left Ventricular Hypertrophy
Published on: September 25, 2017
METTL3 mediates Ang-II-induced cardiac hypertrophy by regulating KLF5 expression in an m6A-dependent manner
Chao Cai1, Yan Jiang2, Yiyan Wang1
1Department of Cardiology, Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, Shiyan City, Hubei Province, China.
Summary
METTL3 promotes cardiac hypertrophy by increasing KLF5 expression via m6A modification. Targeting this METTL3/KLF5 pathway may offer new treatments for heart failure.
Area of Science:
- Cardiovascular Biology
- Epigenetics
- Molecular Medicine
Background:
- Cardiac hypertrophy is a key process in heart failure development, often triggered by Angiotensin II (Ang II).
- The role of METTL3-mediated m6A modification in Ang II-induced cardiac hypertrophy and the involvement of KLF5 are not well understood.
Purpose of the Study:
- To investigate the mechanism by which KLF5 contributes to Ang II-induced myocardial hypertrophy.
- To elucidate the role of METTL3 in regulating KLF5 expression and its impact on cardiac hypertrophy.
Main Methods:
- Established an in vitro model of cardiac hypertrophy using Ang II stimulation of cardiomyocytes.
- Quantified gene and protein expression of METTL3, KLF5, and hypertrophic markers via RT-qPCR and Western blot.
- Validated molecular interactions and mRNA modifications using RIP-qPCR, MeRIP-qPCR, and mRNA stability assays.
Main Results:
- Ang II upregulated METTL3 and KLF5 expression in cardiomyocytes.
- Knockdown of METTL3 or KLF5 attenuated Ang II-induced hypertrophy and suppressed fetal gene expression.
- METTL3 enhanced KLF5 expression and mRNA stability through m6A modification, with KLF5 acting as a downstream effector.
Conclusions:
- METTL3 promotes Ang II-induced cardiac hypertrophy by upregulating KLF5 via an m6A-dependent mechanism.
- The METTL3/KLF5 signaling axis represents a potential therapeutic target for pathological myocardial hypertrophy.
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