Submitted on November 13, 2007
Accepted on February 12, 2008
Human Cardiac Specific cDNA Array for Idiopathic Dilated Cardiomyopathy: Gender Related Differences
Georges E. Haddad1, Lori J. Saunders2, Seth D. Crosby3, Maria Carles2, Federica del Monte4, Kindra King5, Michael R. Bristow6, Francis G. Spinale7, Thomas E. Macgillivray8, Marc J. Semigran9, George William Dec10, Steven A. Williams11, Roger J. Hajjar12, and Judith K. Gwathmey2*
1 Physiology and Biophysics, Howard University, Washington, District of Columbia, United States
2 Gwathmey, Inc, Cambridge, Massachusetts, United States
3 Microarray Core Facility, St. Louis, Missouri, United States
4 Cardiovascular Research Center, Harvard Medical School, Charlestown, Massachusetts, United States
5 Gwathmey Inc., Cambridge, Massachusetts, United States
6 Health Sciences Center, University of Colorado, Denver, Colorado, United States
7 Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina, United States
8 Cardiac Surgery Edwards Research, Massachusetts General Hospital, Boston, Massachusetts, United States
9 Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts, United States
10 Cardiology Division, Massachusetts General Hospital, United States
11 Biological Sciences, Smith College, Northampton, Massachusetts, United States
12 Medicine, Mount Sinai School of Medicine, New York, New York, United States
* To whom correspondence should be addressed. E-mail: jgwathmey{at}gwathmey.com.
Idiopathic dilated cardiomyopathy (IDCM) constitutes a large portion of patients with heart failure of unknown etiology. Up to fifty percent of all transplant recipients carry this clinical diagnosis. Female-specific gene expression in IDCM has not been explored. We report gender-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 non-failing human heart donors. Using 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 up-regulated genes and 18 down-regulated 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 gender specific profile to IDCM. Our observations further suggest for the first time ever novel targets for treatment of IDCM in women and men.
