Physiol. Genomics AJP: Lung Cellular and Molecular Physiology
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Physiol. Genomics 36: 15-23, 2008. First published September 23, 2008; doi:10.1152/physiolgenomics.90296.2008
1094-8341/08 $8.00
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Received 23 July 2008; accepted in final form 21 September 2008.
Physiological Genomics 36:15-23 (2008)
1094-8341/08 $8.00 © 2008 American Physiological Society

Transcriptomic analysis of PPAR{alpha}-dependent alterations during cardiac hypertrophy

Pascal J. H. Smeets 1, Heleen M. de Vogel-van den Bosch 1, Peter H. M. Willemsen 1, Alphons P. Stassen 2, Torik Ayoubi 2, Ger J. van der Vusse 1 and Marc van Bilsen 1

1 Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
2 Clinical Genomics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands

Peroxisome proliferator-activated receptor (PPAR){alpha} regulates lipid metabolism at the transcriptional level and modulates the expression of genes involved in inflammation, cell proliferation, and differentiation. Although PPAR{alpha} has been shown to mitigate cardiac hypertrophy, knowledge about underlying mechanisms and the nature of signaling pathways involved is fragmentary and incomplete. The aim of this study was to identify the processes and signaling pathways regulated by PPAR{alpha} in hearts challenged by a chronic pressure overload by means of whole genome transcriptomic analysis. PPAR{alpha}–/– and wild-type mice were subjected to transverse aortic constriction (TAC) for 28 days, and left ventricular gene expression profile was determined with Affymetrix GeneChip Mouse Genome 430 2.0 arrays containing >45,000 probe sets. In unchallenged hearts, the mere lack of PPAR{alpha} resulted in 821 differentially expressed genes, many of which are related to lipid metabolism and immune response. TAC resulted in a more pronounced cardiac hypertrophy and more extensive changes in gene expression (1,910 and 312 differentially expressed genes, respectively) in PPAR{alpha}–/– mice than in wild-type mice. Many of the hypertrophy-related genes were related to development, signal transduction, actin filament organization, and collagen synthesis. Compared with wild-type hypertrophied hearts, PPAR{alpha}–/– hypertrophied hearts revealed enrichment of gene clusters related to extracellular matrix remodeling, immune response, oxidative stress, and inflammatory signaling pathways. The present study therefore demonstrates that, in addition to lipid metabolism, PPAR{alpha} is an important modulator of immune and inflammatory response in cardiac muscle.

microarray; lipid metabolism; inflammation; immune response






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