Downregulation of myocardial myocyte enhancer factor 2C and myocyte enhancer factor 2C-regulated gene expression in diabetic patients with nonischemic heart failure

• Published in: Circulation (New York, N.Y.) N.Y.), 2002-07, Vol.106 (4), p.407-411
• Main Authors: RAZEGHI, Peter, YOUNG, Martin E, COCKRILL, Tonya C, FRAZIER, O. Howard, TAEGTMEYER, Heinrich
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Calcium - metabolism; Calcium-Transporting ATPases - metabolism; Cardiology. Vascular system; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Diabetic Angiopathies - diagnosis; Diabetic Angiopathies - genetics; Diabetic Angiopathies - metabolism; DNA-Binding Proteins - metabolism; Down-Regulation; Energy Metabolism; Female; Glucose Transporter Type 4; Heart; Heart Failure - diagnosis; Heart Failure - genetics; Heart Failure - metabolism; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; MADS Domain Proteins; Male; Medical sciences; MEF2 Transcription Factors; Middle Aged; Monosaccharide Transport Proteins - biosynthesis; Monosaccharide Transport Proteins - genetics; Muscle Proteins; Myocardium - metabolism; Myogenic Regulatory Factors - genetics; Myogenic Regulatory Factors - metabolism; Myosin Heavy Chains - biosynthesis; Myosin Heavy Chains - genetics; Retrospective Studies; RNA, Messenger - biosynthesis; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Transcription Factors - metabolism; Transcription, Genetic; Troponin I - biosynthesis; Troponin I - genetics
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000026392.80723.DC

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. 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 Ca(2+)-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. 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.