Published Online
on July 1, 2002

A more recent version of this article appeared on July 23, 2002

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Submitted on April 2, 2002
Revised on May 28, 2002
Accepted on June 5, 2002

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, and 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.

^* To whom correspondence should be addressed. 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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