title: Receptor-interacting protein 140 overexpression impairs cardiac mitochondrial function and accelerates the transition to heart failure in chronically infarcted rats.
abstract: Heart failure (HF) is associated with myocardial energy metabolic abnormality. Receptor-interacting protein 140 (RIP140) is an important transcriptional cofactor for maintaining energy balance in high-oxygen consumption tissues. However, the role of RIP140 in the pathologic processes of HF remains to be elucidated. In this study, we investigated the role of RIP140 in mitochondrial and cardiac functions in rodent hearts under myocardial infarction (MI) stress. MI was created by a permanent ligation of left anterior descending coronary artery and exogenous expression of RIP140 by adenovirus (Ad) vector delivery. Four weeks after MI or Ad-RIP140 treatment, cardiac function was assessed by echocardiographic and hemodynamics analyses, and the mitochondrial function was determined by mitochondrial genes expression, biogenesis, and respiration rates. In Ad-RIP140 or MI group, a subset of metabolic genes changed, accompanied with slight reductions in mitochondrial biogenesis and respiration rates but no change in adenosine triphosphate (ATP) content. Cardiac malfunction was compensated. However, under MI stress, rats overexpressing RIP140 exhibited greater repressions in mitochondrial genes, state 3 respiration rates, respiration control ratio, and ATP content and had further deteriorated cardiac malfunction. In conclusion, RIP140 overexpression leads to comparable cardiac function as resulted from MI, but RIP140 aggravates metabolic repression, mitochondrial malfunction, and further accelerates the transition to HF in response to MI stress.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Pharmacy, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China; National and Local United Engineering Laboratory of Druggability and New Drug Evaluation, Guangzhou, People's Republic of China.
authors.forename: YanFang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China; National and Local United Engineering Laboratory of Druggability and New Drug Evaluation, Guangzhou, People's Republic of China.
authors.forename: ShaoRui
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: ZhongBao
authors.initials: Z
authors.lastname: Yue
authors.affiliation: Division of Cardiology, and Institute of Stem Cell and Regenerative Medicine, School of Medicine, University of Washington, Seattle, Wash.
authors.forename: YiQiang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: ChangHua
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: WeiWei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: LuanKun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China; National and Local United Engineering Laboratory of Druggability and New Drug Evaluation, Guangzhou, People's Republic of China. Electronic address: liupq@mail.sysu.edu.cn.
authors.forename: PeiQing
authors.initials: P
authors.lastname: Liu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D019069:Cell Respiration; D002908:Chronic Disease; D004562:Electrocardiography; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005822:Genetic Vectors / Q000378:metabolism; D006333:Heart Failure / Q000150:complications* / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006439:Hemodynamics; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000648:ultrastructure; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D056971:Nuclear Receptor Co-Repressor 1 / Q000378:metabolism*; D001678:Organelle Biogenesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018487:Ventricular Dysfunction, Left
chemical_list: D056971:Nuclear Receptor Co-Repressor 1; D012333:RNA, Messenger; D000255:Adenosine Triphosphate