Open AccessICS II protects against cardiac hypertrophy by regulating metabolic remodelling, not by inhibiting autophagy
Author(s) -
Han Dongjian,
Wang Bo,
Cui Xinyue,
He Weiwei,
zhang Yi,
Jiang Qingjiao,
Wang Fuhang,
Liu Zhiyu,
Shen Deliang
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16175
Subject(s) - angiotensin ii , muscle hypertrophy , medicine , pressure overload , autophagy , endocrinology , heart failure , sirt3 , cardiac function curve , ventricular remodeling , oxidative stress , ampk , ketone bodies , cardiac hypertrophy , chemistry , apoptosis , metabolism , blood pressure , biochemistry , enzyme , protein kinase a , sirtuin , nad+ kinase
Cardiac hypertrophy is characterized by a shift in metabolic substrate utilization. Therefore, the regulation of ketone body uptake and metabolism may have beneficial effects on heart injuries that induce cardiac remodelling. In this study, we investigated whether icariside II (ICS II) protects against cardiac hypertrophy in mice and cardiomyocytes. To create cardiac hypertrophy animal and cell models, mice were subjected to transverse aortic constriction (TAC), and embryonic rat cardiomyocytes (H9C2) were stimulated with angiotensin II, a neurohumoral stressor. Both the in vivo and in vitro results suggest that ICS II treatment ameliorated pressure overload–induced cardiac hypertrophy and preserved heart function. In addition, apoptosis and oxidative stress were reduced in the presence of ICS II. Moreover, ICS II inhibited excess autophagy in TAC‐induced hearts and angiotensin II–stimulated cardiomyocytes. Mechanistically, we found that ICS II administration regulated SIRT3 expression in cardiac remodelling. SIRT3 activation increased ketone body transportation and utilization. Collectively, our data show that ICS II attenuated cardiac hypertrophy by modulating ketone body and fatty acid metabolism, and that this was likely due to the activation of the SIRT3‐AMPK pathway. ICS II treatment may provide a new therapeutic strategy for improving myocardial metabolism in cardiac hypertrophy and heart failure.