Downregulation of myocardial myocyte enhancer factor 2C and myocyte enhancer factor 2C-regulated gene expression in diabetic patients with nonischemic heart failure
Downregulation of myocardial myocyte enhancer factor 2C and myocyte enhancer factor 2C-regulated gene expression in diabetic patients with nonischemic heart failure
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DOI：
10.1161/01.cir.0000026392.80723.dc
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发表时间：
2002-07-23
期刊：
影响因子：
37.8
通讯作者：
Taegtmeyer, H
中科院分区：
文献类型：
--
作者：
Razeghi, P;Young, ME;Taegtmeyer, H
背景-在动物研究中，糖尿病已被证明可诱导心脏能量代谢和钙稳态关键调节因子基因表达的变化。在本研究中，我们测试的假设，即代谢基因表达在非缺血性衰竭的糖尿病患者的心脏不同，在非缺血性衰竭的心脏nondiabeticpatients.Methods和Results-Left心室组织从nonfailing心脏（n=6）和非缺血性衰竭的心脏患者有或无2型糖尿病。能量底物代谢关键调节因子的心肌转录水平（葡萄糖转运蛋白1、葡萄糖转运蛋白4、丙酮酸脱氢酶激酶4、过氧化物酶体增殖物激活受体α、肌肉肉毒碱棕榈酰转移酶-1、中链酰基辅酶A脱氢酶和解偶联蛋白3）、钙稳态（肌浆网Ca 2 +-ATP酶[SERCA 2a]、受磷蛋白和心肌兰尼碱受体），和收缩功能（肌球蛋白重链α）使用实时定量逆转录聚合酶链反应测量。此外，我们测量了肌细胞增强因子2C（MEF 2C）和SERCA 2a蛋白水平。与非糖尿病组相比，糖尿病组中只有MEF 2C调节的转录物（葡萄糖转运蛋白4、SERCA 2a和肌球蛋白重链α）较低。结论MEF 2C及其调控基因在糖尿病心力衰竭患者中表达减少。这种转录机制可能与糖尿病心力衰竭患者的收缩功能障碍有关。
Background-In animal studies, diabetes has been shown to induce changes in gene expression of key regulators in cardiac energy metabolism and calcium homeostasis. In the present study, we tested the hypothesis that metabolic gene expression in nonischemic failing hearts of diabetic patients differs from that in nonischemic failing hearts of nondiabetic patients.Methods and Results-Left ventricular tissue was obtained from nonfailing hearts (n=6) and from nonischemic failing hearts of patients with or without type 2 diabetes. Myocardial transcript levels of key regulators in energy substrate metabolism (glucose transporter 1, glucose transporter 4, pyruvate dehydrogenase kinase 4, peroxisome proliferator-activated receptor alpha, muscle carnitine palmitoyl transferase-1, medium-chain acyl-CoA dehydrogenase, and uncoupling protein 3), calcium homeostasis (sarcoplasmic reticulum Ca2+-ATPase [SERCA2a], phospholamban, and cardiac ryanodine receptor), and contractile function (myosin heavy chain alpha) were measured using real-time quantitative reverse transcription-polymerase chain reaction. In addition, we measured myocyte enhancer factor 2C (MEF2C) and SERCA2a protein levels. Only MEF2C regulated transcripts (glucose transporter 4, SERCA2a, and myosin heavy chain alpha) were lower in the diabetic group compared with the nondiabetic group. MEF2C protein content was also decreased.Conclusion-MEF2C and MEF2C-regulated genes are decreased in the failing hearts of diabetic patients. This transcriptional mechanism may contribute to the contractile dysfunction in heart failure patients with diabetes.