title: Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction.
abstract: Testosterone can affect cardiovascular disease, but its effects on mitochondrial dynamics in the post-infarct myocardium remain unclear. To observe the effects of testosterone replacement, a rat model of castration-myocardial infarction (MI) was established by ligating the left anterior descending coronary artery 2 weeks after castration with or without testosterone treatment. Expression of mitochondrial fission and fusion proteins was detected by western blot and immunofluorescence 14 days after MI. Cardiac function, myocardial inflammatory infiltration and fibrosis, cardiomyocyte apoptosis, mitochondrial microstructure, and ATP levels were also assessed. Compared with MI rats, castrated rats showed aggravated mitochondrial and myocardial insults, including mitochondrial swelling and disordered arrangement; loss of cristae, reduced mitochondrial length; decreased ATP levels; cardiomyocyte apoptosis; and impaired cardiac function. Results of western blotting analyses indicated that castration downregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) and mitofusin 2, but upregulated dynamin-related protein 1. The results were also supported by results obtained using immunofluorescence. However, these detrimental effects were reversed by testosterone supplementation, which also elevated the upstream AMP-activated protein kinase (AMPK) activation of PGC1A. Thus, testosterone can protect mitochondria in the post-infarct myocardium, partly via the AMPK-PGC1A pathway, thereby decreasing mitochondrial dysfunction and cardiomyocyte apoptosis. The effects of testosterone were confirmed by the results of ELISA analyses.
authors.affiliation: Laboratory of Cardiovascular Internal Medicine Department First Affiliated Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang 150001, China Laboratory of Cardiovascular Internal Medicine Department The Heilongjiang Province Hospital, 82 Zhongshan Lu, Xiangfang District, Harbin, Heilongjiang 150001, China.
authors.forename: Fengyue
authors.initials: F
authors.lastname: Wang
authors.affiliation: Laboratory of Cardiovascular Internal Medicine Department First Affiliated Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang 150001, China Laboratory of Cardiovascular Internal Medicine Department The Heilongjiang Province Hospital, 82 Zhongshan Lu, Xiangfang District, Harbin, Heilongjiang 150001, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Laboratory of Cardiovascular Internal Medicine Department First Affiliated Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang 150001, China Laboratory of Cardiovascular Internal Medicine Department The Heilongjiang Province Hospital, 82 Zhongshan Lu, Xiangfang District, Harbin, Heilongjiang 150001, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Sun
authors.affiliation: Laboratory of Cardiovascular Internal Medicine Department First Affiliated Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang 150001, China Laboratory of Cardiovascular Internal Medicine Department The Heilongjiang Province Hospital, 82 Zhongshan Lu, Xiangfang District, Harbin, Heilongjiang 150001, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Laboratory of Cardiovascular Internal Medicine Department First Affiliated Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang 150001, China Laboratory of Cardiovascular Internal Medicine Department The Heilongjiang Province Hospital, 82 Zhongshan Lu, Xiangfang District, Harbin, Heilongjiang 150001, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Laboratory of Cardiovascular Internal Medicine Department First Affiliated Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang 150001, China Laboratory of Cardiovascular Internal Medicine Department The Heilongjiang Province Hospital, 82 Zhongshan Lu, Xiangfang District, Harbin, Heilongjiang 150001, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
authors.affiliation: Laboratory of Cardiovascular Internal Medicine Department First Affiliated Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang 150001, China Laboratory of Cardiovascular Internal Medicine Department The Heilongjiang Province Hospital, 82 Zhongshan Lu, Xiangfang District, Harbin, Heilongjiang 150001, China fulunadia@aliyun.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Fu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D020249:Hormone Replacement Therapy; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000008:administration & dosage*
chemical_list: D047495:PPAR gamma; D013739:Testosterone; D000255:Adenosine Triphosphate; D055372:AMP-Activated Protein Kinases
keywords: AMPK; ATP; PGC1A; mitochondrial dynamics; myocardial infarction; testosterone