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Human cardiac-specific cDNA array for idiopathic dilated cardiomyopathy: sex-related differences

¹ Department of Physiology and Biophysics, College of Medicine, Howard University, Washington, District of Columbia
² Gwathmey, Incorporated, Cambridge, Massachusetts
³ Microarray Core Facility, Washington University Medical School, St. Louis, Missouri
⁴ Cardiovascular Research Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts
⁵ Division of Cardiology, School of Medicine, University of Colorado Health Sciences Center, Denver, Colorado
⁶ Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina
⁷ Cardiac Surgery, Edwards Research
⁸ Cardiology Division, Gray/Bigelow, Massachusetts General Hospital, Boston
¹⁰ Department of Biological Sciences, Smith College, Northampton, Massachusetts
⁹ Cardiovascular Research Center, Mount Sinai School of Medicine, New York, New York
¹¹ Boston University School of Medicine, Cambridge, Massachusetts

Idiopathic dilated cardiomyopathy (IDCM) constitutes a large portion of patients with heart failure of unknown etiology. Up to 50% of all transplant recipients carry this clinical diagnosis. Female-specific gene expression in IDCM has not been explored. We report sex-related differences in the gene expression profile of ventricular myocardium from patients undergoing cardiac transplantation. We produced and sequenced subtractive cDNA libraries, using human left ventricular myocardium obtained from male transplant recipients with IDCM and nonfailing human heart donors. With the resulting sequence data, we generated a custom human heart failure microarray for IDCM containing 1,145 cardiac-specific oligonucleotide probes. This array was used to characterize RNA samples from female IDCM transplant recipients. We identified a female gene expression pattern that consists of 37 upregulated genes and 18 downregulated genes associated with IDCM. Upon functional analysis of the gene expression pattern, deregulated genes unique to female IDCM were those that are involved in energy metabolism and regulation of transcription and translation. For male patients we found deregulation of genes related to muscular contraction. These data suggest that 1) the gene expression pattern we have detected for IDCM may be specific for this disease and 2) there is a sex-specific profile to IDCM. Our observations further suggest for the first time ever novel targets for treatment of IDCM in women and men.

gene expression; heart failure; IDCM markers