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 tis...
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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.
刘秀凤,郑友祥(阜宁县中医院,江苏阜宁224400)20世纪70年代末,药物专家根据人体胆固醇生物合成的机制,开始筛选胆固醇合成限速酶——3羟3甲基戊二酸单酰辅酶A(hydroxymethylglutaryl coenzyme A reductaseinhibitor,HMG—CoA)...
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刘秀凤,郑友祥(阜宁县中医院,江苏阜宁224400)
20世纪70年代末,药物专家根据人体胆固醇生物合成的机制,开始筛选胆固醇合成限速酶——3羟3甲基戊二酸单酰辅酶A(hydroxymethylglutaryl coenzyme A reductaseinhibitor,HMG—CoA)还原酶抑制剂。经过十多年的努力,1987年,第一个他汀品种上市并获美国国家食品药品监督管理局(Foodand Drug Administration,FDA)批准。
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