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(Circulation. 2002;106:407.)
© 2002 American Heart Association, Inc.

Brief Rapid Communications

Downregulation of Myocardial Myocyte Enhancer Factor 2C and Myocyte Enhancer Factor 2C–Regulated Gene Expression in Diabetic Patients With Nonischemic Heart Failure

Peter Razeghi, MD; Martin E. Young, DPhil; Tonya C. Cockrill, MS; O. Howard Frazier, MD; Heinrich Taegtmeyer, MD, DPhil

From the Division of Cardiology, University of Texas–Houston Medical School (P.R., M.E.Y., T.C.C., H.T.), and St Luke’s Episcopal Hospital and Texas Heart Institute (O.H.F., H.T.), Houston, Tex.

Correspondence to Heinrich Taegtmeyer, MD, DPhil, Department of Internal Medicine, Division of Cardiology, University of Texas Houston–Medical School, 6431 Fannin, MSB 1.246, Houston, TX 77030. E-mail Heinrich.Taegtmeyer{at}uth.tmc.edu

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 , 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 ) 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 ) 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.

Key Words: diabetes mellitus • cardiomyopathy • metabolism • polymerase chain reaction

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