miR-182 Modulates Myocardial Hypertrophic Response Induced by Angiogenesis in Heart

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Angiogenesis Research

Background:

• Myocardial hypertrophy is an adaptive response to increased hemodynamic load.
• Cardiac angiogenesis, while supporting increased heart mass, can also promote hypertrophy.
• Endothelial-derived nitric oxide (NO) mediates placental growth factor (PlGF)-induced hypertrophy via Regulator of G protein signaling 4 (RGS4) and Akt/mTORC1 pathways.

Purpose of the Study:

• To investigate the role of microRNAs (miRNAs) in myocardial hypertrophy associated with angiogenesis.
• To identify specific miRNAs involved in the crosstalk between endothelial cells and cardiomyocytes during hypertrophic responses.

Main Methods:

• Utilized placental growth factor (PlGF) mouse models and nitric oxide (NO)-treated cardiomyocytes.
• Assessed miR-182 expression levels in relation to hypertrophy and specific molecular pathways.
• Employed anti-miR-182 treatment and targeted gene depletion (Bcat2) to evaluate functional effects.

Main Results:

• miR-182 was upregulated concurrently with hypertrophy in PlGF mice, but not when hypertrophy was blocked or in eNOS(-/-) mice.
• Anti-miR-182 treatment inhibited hypertrophy and Akt/mTORC1 activation in PlGF mice and cardiomyocytes.
• miR-182 targets Bcat2, Foxo3, and Adcy6; Bcat2 depletion promoted cardiomyocyte hypertrophy via Akt/mTORC1 activation.

Conclusions:

• miR-182 is a novel mediator in the endothelial-cardiomyocyte crosstalk during angiogenesis-induced myocardial hypertrophy.
• miR-182 plays a critical role in promoting hypertrophic responses, partly through targeting Bcat2.
• This pathway is specific to angiogenesis-induced hypertrophy, as evidenced by lack of miR-182 upregulation in pressure overload models.