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Published Online
on February 24, 2003

Hypertension. 2003
Published online before print February 24, 2003, doi: 10.1161/01.HYP.0000057573.32425.95
A more recent version of this article appeared on March 1, 2003
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Submitted on September 25, 2002
Revised on October 16, 2002

Cardiac Transcriptome Analysis in Obesity-Related Hypertension

Pierre Philip-Couderc; Fatima Smih; Michel Pelat; Cyril Vidal; Patrick Verwaerde; Atul Pathak; Sophie Buys; Michel Galinier; Jean-Michel Senard; and Philippe Rouet*

From INSERM U586, Faculté de Médecine, Laboratoire de Pharmacologie Médicale et Clinique, Toulouse Cedex, France.

* To whom correspondence should be addressed. E-mail: Philippe.rouet{at}toulouse.inserm.fr.

Abstract--Obesity is associated with volumetric arterial hypertension and with early increase in heart rate and decreased heart rate variability. The consequences of obesity-related hypertension on heart gene regulation are poorly known and were investigated in a model of obesity-related hypertension induced by high fat diet in dogs. When compared with control animals (n=6), a 9-week high fat diet (n=6) provoked significant weight gain and increased blood pressure load and heart rate but failed to significantly change left ventricular mass assessed by echocardiography. Subtractive hybridization of dog heart cDNA libraries were used to generate sublibraries containing differentially expressed cDNAs that were in turn spotted onto membranes to create custom microarrays. Hybridizations of these microarrays with complex probes representing mRNAs expressed in right atria and left ventricles from obese hypertensive and control dogs were performed. Thirty-eight differentially expressed genes were identified; altered expression was confirmed by Northern blot analysis in 15. In addition, real-time quantitative polymerase chain reaction confirmed differential expression for 80% of the randomly chosen tested genes. Once identified, transcripts were categorized into groups involved in metabolism, cell signaling, ionic regulation, cell proliferation, protein synthesis, and tissue remodeling. In addition, we found a set of 11 cDNAs encoding proteins with unknown functions. This study clearly shows that obesity-related hypertension, lasting for only 9 weeks, causes marked changes in gene expression in right atrium as well as the left ventricle that may contribute to early functional changes in heart function and to long-term structural changes such as left ventricular hypertrophy and remodeling.


Key words: obesity • hypertension, arterial • heart rate • heart • dogs




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