Choline ameliorates cardiac hypertrophy by regulating metabolic remodelling and UPRmt through SIRT3-AMPK pathway

Cardiovascular Research
Man XuWei-Jin Zang

Abstract

Cardiac hypertrophy is characterised by a shift in metabolic substrate utilisation, but the molecular events underlying the metabolic remodelling remain poorly understood. We explored metabolic remodelling and mitochondrial dysfunction in cardiac hypertrophy and investigated the cardioprotective effects of choline. The experiments were conducted using a model of ventricular hypertrophy by partially banding the abdominal aorta of Sprague Dawley rats. Cardiomyocyte size and cardiac fibrosis were significantly increased in hypertrophic hearts. In vitro cardiomyocyte hypertrophy was induced by exposing neonatal rat cardiomyocytes to angiotensin II (Ang II) (10-6 M, 24 h). Choline attenuated the mito-nuclear protein imbalance and activated the mitochondrial unfolded protein response (UPRmt) in the heart, thereby preserving the ultrastructure and function of mitochondria in the context of cardiac hypertrophy. Moreover, choline inhibited myocardial metabolic dysfunction by promoting the expression of proteins involved in ketone body and fatty acid metabolism in response to pressure overload, accompanied by the activation of sirtuin 3/AMP-activated protein kinase (SIRT3-AMPK) signalling. In vitro analyses demonstrated that SIRT3 siRNA ...Continue Reading

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Citations

Sep 10, 2019·Aging·Jiahao DuanChun Yang
Mar 28, 2020·Korean Circulation Journal·Chang Myung OhYangsoo Jang
Jan 25, 2020·Current Neuropharmacology·Huidan WengQinyong Ye
Dec 17, 2020·Frontiers in Cardiovascular Medicine·Yan WangChen Liu
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Dec 22, 2020·Free Radical Biology & Medicine·Li ZhuLinxi Chen
Mar 3, 2021·Laboratory Investigation; a Journal of Technical Methods and Pathology·Xi HeWei-Jin Zang
Jul 3, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Andrea Del CampoHugo E Verdejo

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