Liu Depei Team Revealed the Regulating Effect of Sirtuin SAC2 on Metabolic Homeostasis to Inhibit Aging-related Cardiac Hypertrophy


Circulation, an international top cardiovascular journal, published a paper entitled “SIRT2 Acts as a Cardioprotective Deacetylase in Pathological Cardiac Hypertrophy” by Academician Liu Depei and Chen Houzao from the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, revealing that the protein deacetylase SIRT2 inhibits senescence-associated cardiac hypertrophy by regulating metabolic homeostasis.


Cardiovascular disease has already been the leading cause of death in humans around the world. Among population over 65 years old, cardiovascular disease (such as hypertension and atherosclerosis and subsequent heart failure and stroke) leads to more than 40% of deaths and more than 80% of all cardiovascular deaths occur among the population over 65 years old. Advanced age is the main risk factor for cardiovascular disease, and in elderly cardiovascular patients, the prognosis of the disease becomes worse with the increase of age. However, at present, we have little knowledge of variation in the structure and function of cardiovascular system during aging. Further understanding of aging-related heart diseases is instrumental to guiding clinical prevention and treatment of senile cardiovascular diseases such as cardiac hypertrophy and heart failure.


Academician Liu Depei’s lab has long been devoted to the study of major diseases related to aging, especially cardiovascular diseases. In 2016, Liu Depei's team revealed that protein deacylase SIRT1 can inhibit aging-related abdominal aortic aneurysms (Circ Res. 2016 Oct 28; 119 (10): 1076-1088.), and participate in the protective effect of energy limitation on abdominal aortic aneurysm (J Exp Med. 2016 Oct 17; 213 (11): 2473-2488). In this study, Liu Depei's team found the core deacetylases involved in aging-related cardiac hypertrophy. With the natural aging model and angiotensin II-induced age-related cardiac hypertrophy model, the author found that increased angiotensin II during senescence can activate c-Src kinase and c-Src can promote the degradation of protein deacetylase SIRT2. SIRT2, a protein deacylase, can deacetylate histones and non-histones to participate in several physiological and pathological processes such as tumor, metabolism and inflammation. In this study, the author found that SIRT2 protein interacted with kinase LKB1 to deacetylate LKB1 at K48 locus to activate AMPK, thus regulating homeostasis to protect cardiac function and inhibiting age-related cardiac hypertrophy and myocardial fibrosis. At the same time, this study also found that metformin’s impact on AMPK activation and inhibition of cardiac hypertrophy dependents on the SIRT2 protein. This study further enriches our knowledge of how aging regulates metabolic-related epigenetic modifying enzymes to promote aging-related cardiac hypertrophy. It also suggests that SIRT2 may be a potential target for the treatment of aging-related cardiac hypertrophy, which provides an important theoretical basis for further exploring the treatment of aging-related cardiovascular diseases.



Liu Depei (Academician) and Chen Houzao (Researcher) are co-corresponding authors of this study. Dr. Tang Xiaoqiang and Chen Xiaofeng (a doctoral student of 2016 grade) of Liu Depei’s team are co-first authors. This research is sponsored by Key Projects and Outstanding Youth Project of NSFC, Youth Yangtze River Project of Ministry of Education, Ten Thousand Talents Program of Organization Department of the Central Committee of the CPC and CAMS Innovation Fund for Medical Sciences (2017-I2M-1-008).






(Institute of Basic Medical Sciences)