HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Chen, H. Articles by Sepulveda, J. L. Search for Related Content PubMed PubMed Citation Articles by Chen, H. Articles by Sepulveda, J. L.

Gene expression changes associated with fibronectin-induced cardiac myocyte hypertrophy

¹ Departments of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213
² Cardiovascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213

Fibronectin (FN) is an extracellular matrix protein that binds to integrin receptors and couples cardiac myocytes to the basal lamina. Cardiac FN expression is elevated in models of pressure overload, and FN causes cultured cardiac myocytes to hypertrophy by a mechanism that has not been characterized in detail. In this study, we analyzed the gene expression changes induced by FN in purified rat neonatal ventricular myocytes using the Affymetrix RAE230A microarray, to understand how FN affects gene expression in cardiac myocytes and to separate the effects contributed by cardiac nonmyocytes in vivo. Pathway analysis using z-score statistics and comparison with a mouse model of cardiac hypertrophy revealed several pathways stimulated by FN in cardiac myocytes. In addition to the known cardiac myocyte hypertrophy markers, FN significantly induced metabolic pathways including virtually all of the enzymes of cholesterol biosynthesis, fatty acid biosynthesis, and the mitochondrial electron transport chain. FN also increased the expression of genes coding for ribosomal proteins, translation factors, and the ubiquitin-proteasome pathway. Interestingly, cardiac myocytes plated on FN showed elevated expression of the fibrosis-promoting peptides connective tissue growth factor (CTGF), WNT1 inducible signaling pathway protein 2 (WISP2), and secreted acidic cysteine-rich glycoprotein (SPARC). Our data complement in vivo studies and reveal several novel genes and pathways stimulated by FN, pointing to cardiac myocyte-specific mechanisms that lead to development of the hypertrophic phenotype.

extracellular matrix; integrin; ventricular remodeling; signal transduction; gene expression profiling

This article has been cited by other articles:

				S. V. de Sa, M. L. Correa-Giannella, M. C. Machado, K. Krogh, M. Q. de Almeida, M. A. Albergaria Pereira, S. A. Coelho Siqueira, R. A. Patzina, F. S. Ibuki, M. C. Sogayar, et al. Serpin Peptidase Inhibitor Clade A Member 1 as a Potential Marker for Malignancy in Insulinomas Clin. Cancer Res., September 15, 2007; 13(18): 5322 - 5330. [Abstract] [Full Text] [PDF]

				D. Stilli, L. Bocchi, R. Berni, M. Zaniboni, F. Cacciani, C. Chaponnier, E. Musso, G. Gabbiani, and S. Clement Correlation of {alpha}-skeletal actin expression, ventricular fibrosis and heart function with the degree of pressure overload cardiac hypertrophy in rats Exp Physiol, May 1, 2006; 91(3): 571 - 580. [Abstract] [Full Text] [PDF]

				G. Bianchi Genetic variations of tubular sodium reabsorption leading to "primary" hypertension: from gene polymorphism to clinical symptoms Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1536 - R1549. [Abstract] [Full Text] [PDF]

				M. Liang and B. Ventura Physiological genomics in PG and beyond: July to September 2005 Physiol Genomics, October 17, 2005; 23(2): 119 - 124. [Full Text] [PDF]