RIP140 overexpression impairs cardiac mitochondrial function and accelerates the transition to heart failure in chronically infarcted rats
Heart failure 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 on pathological processes of heart failure 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 permanent ligation of left anterior descending coronary artery(LAD)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 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(RCR),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 heart failure in response to MI stress.
RIP140 heart failure energy metabolism mitochondria Adenovirus
YanFang Chen ShaoRui Chen ZhongBao Yue YiQiang Zhang ChangHua Zhou WeiWei Cao Xi Chen LuanKun Zhang PeiQing Liu
Department of Pharmacology and Toxicology,School of Pharmaceutical Sciences,Sun Yat-sen University,G Department of Pharmacology and Toxicology,School of Pharmaceutical Sciences,Sun Yat-sen University,G Department of Pharmacology and Toxicology,School of Pharmaceutical Sciences,Sun Yat-sen University,G Division of Cardiology,and Institute of Stem Cell and Regenerative Medicine,School of Medicine,Unive
国内会议
广州
英文
1-16
2016-12-17（万方平台首次上网日期，不代表论文的发表时间）