Small-molecule 7,8-dihydroxyflavone counteracts compensated and decompensated cardiac hypertrophy via AMPK activation  

作　　者：Peng-Zhou HANG Pei-Feng LI Jie LIU Feng-Feng LI Ting-Ting CHEN Yang PAN Man-Ru ZHANG Hua-Qing YU Hong-Yu JI Zhi-Min DU Jing ZHAO 

机构地区：[1]Institute of Clinical Pharmacology,the Second Affiliated Hospital of Harbin Medical University(University Key Laboratory of Drug Research,Heilongjiang Province),Harbin,China [2]Department of Pharmacy,Clinical Medical College,Yangzhou University,Northern Jiangsu People's Hospital,Yangzhou,China [3]Department of Pharmacology,Harbin Medical University,Harbin,China [4]State Key Laboratory of Quality Research in Chinese Medicines,Macao University of Science and Technology,Macao,China [5]Department of Cardiology,the First Affiliated Hospital of Harbin Medical University,Harbin,China

出　　处：《Journal of Geriatric Cardiology》2022年第11期853-866,共14页老年心脏病学杂志（英文版）

基　　金：supported by the National Natural Science Foundation of China (No. 82070309, 8187 0191, and 82073838);“333 Project” of Jiangsu Province;the Lvyangjinfeng Talent Program of Yangzhou

摘　　要：BACKGROUND Pathological cardiac hypertrophy is a compensated response to various stimuli and is considered a key risk factor for heart failure.7,8-Dihydroxyflavone(7,8-DHF)is a flavonoid derivative that acts as a small-molecule brain-derived neurotrophic factor mimetic.The present study aimed to explore the potential role of 7,8-DHF in cardiac hypertrophy.METHODS Kunming mice and H9c2 cells were exposed to transverse aortic constriction or isoproterenol(ISO)with or without 7,8-DHF,respectively.F-actin staining was performed to calculate the cell area.Transcriptional levels of hypertrophic markers,including ANP,BNP,andβ-MHC,were detected.Echocardiography,hematoxylin-eosin staining,and transmission electron microscopy were used to examine the cardiac function,histology,and ultrastructure of ventricles.Protein levels of mitochondria-related factors,such as adenosine monophosphate-activated protein kinase(AMPK),and peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α),were detected.RESULTS 7,8-DHF inhibited compensated and decompensated cardiac hypertrophy,diminished the cross-sectional area,and alleviated the mitochondrial disorders of cardiomyocytes.Meanwhile,7,8-DHF reduced the cell size and repressed the mRNA levels of the hypertrophic markers of ISO-treated cardiomyocytes.In addition,7,8-DHF activated AMPK and PGC-1αsignals without affecting the protein levels of mitochondrial dynamics-related molecules.The effects of 7,8-DHF were eliminanted by Compound C,an AMPK inhibitor.CONCLUSIONS These findings suggest that 7,8-DHF inhibited cardiac hypertrophy and mitochondrial dysfunction by activating AMPK signaling,providing a potential agent for the treatment of pathological cardiac hypertrophy.

关 键 词：CARDIAC HYPERTROPHY inhibited 

分 类 号：R542.2[医药卫生—心血管疾病]