Human Cardiac-Specific cDNA Array for Idiopathic Dilated Cardiomyopathy: Sex-Related Differences

Authors

Georges E. Haddad, Howard University
Lori J. Saunders, Gwathmey, Inc.
Seth D. Crosby, Washington University School of Medicine in St. Louis
Maria Carles, Gwathmey, Inc.
Federica Del Monte, Beth Israel Deaconess Medical Center
Kindra King, Gwathmey, Inc.
Michael R. Bristow, University of Colorado Anschutz Medical Campus
Francis G. Spinale, Medical University of South Carolina
Thomas E. Macgillivray, Massachusetts General Hospital
Marc J. Semigran, Massachusetts General Hospital
G. William Dec, Massachusetts General Hospital
Steven A. Williams, Smith CollegeFollow
Roger J. Hajjar, Icahn School of Medicine at Mount Sinai
Judith K. Gwathmey, Gwathmey, Inc.

Document Type

Article

Publication Date

4-22-2008

Publication Title

Physiological Genomics

Abstract

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.

Keywords

Gene expression, Heart failure, IDCM markers

Volume

33

Issue

2

First Page

267

Last Page

277

DOI

10.1152/physiolgenomics.00265.2007

ISSN

10948341

Rights

© 2008 the American Physiological Society

Comments

Archived as published. Open access paper.

Recommended Citation

Haddad, Georges E.; Saunders, Lori J.; Crosby, Seth D.; Carles, Maria; Del Monte, Federica; King, Kindra; Bristow, Michael R.; Spinale, Francis G.; Macgillivray, Thomas E.; Semigran, Marc J.; Dec, G. William; Williams, Steven A.; Hajjar, Roger J.; and Gwathmey, Judith K., "Human Cardiac-Specific cDNA Array for Idiopathic Dilated Cardiomyopathy: Sex-Related Differences" (2008). Biological Sciences: Faculty Publications, Smith College, Northampton, MA.
https://scholarworks.smith.edu/bio_facpubs/166