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Macroarray analysis in the hypertrophic left ventricle of renin-dependent hypertensive rats: identification of target genes for renin

EA 3740, Laboratoire de Pharmacologie, Génomique fonctionnelle dans l'athéro-thrombose, Université Claude Bernard-Lyon1, UFR de Médecine RTH Laennec, rue Guillaume Paradin, 69372 Lyon cedex 08, France

Catherine Cerutti

EA 3740, Laboratoire de Pharmacologie, Génomique fonctionnelle dans l'athéro-thrombose, Université Claude Bernard-Lyon1, UFR de Médecine RTH Laennec, rue Guillaume Paradin, 69372 Lyon cedex 08, France

Jacques Randon

EA 3740, Laboratoire de Pharmacologie, Génomique fonctionnelle dans l'athéro-thrombose, Université Claude Bernard-Lyon1, UFR de Médecine RTH Laennec, rue Guillaume Paradin, 69372 Lyon cedex 08, France

Lilian McGregor

EA 3740, Laboratoire de Pharmacologie, Génomique fonctionnelle dans l'athéro-thrombose, Université Claude Bernard-Lyon1, UFR de Médecine RTH Laennec, rue Guillaume Paradin, 69372 Lyon cedex 08, France

Giampiero Bricca

EA 3740, Laboratoire de Pharmacologie, Génomique fonctionnelle dans l'athéro-thrombose, Université Claude Bernard-Lyon1, UFR de Médecine RTH Laennec, rue Guillaume Paradin, 69372 Lyon cedex 08, France, bricca@lyon. inserm.fr

Introduction The aim of this work was to identify new renin target genes in left ventricular hypertrophy during hypertension.

Materials and methods We compared left ventricle gene expression from four transgenic TGR(mRen2)27 (TG+/-) rats and four non-transgenic littermates (TG-/-) using cDNA macroarray. Hybridisation signals were quantified with a phosphorimager, and normalised to an external scale. Data analysis was performed with Statistical Analysis for Microarrays (SAM 1.21) software. The mRNA levels of candidate genes were determined by semi-quantitative RT-PCR in three different hypertensive rats: TG+/-, spontaneously hypertensive (SHR) and genetically Lyon hypertensive (LH) rats, compared to their respective controls (TG-/-, Wistar-Kyoto, Lyon low blood pressure rats).

Results Out of 1,200 genes present on the macroarray, 233 were reliably measured and only three were overexpressed (Biglycan, β1-adenosine monophosphate-activated protein kinase [AMPK] and amyloid precursor like protein 2 [APLP2]) and 19 were underexpressed in the left ventricle of TG+/compared with TG-/-. APLP2 is a member of the amyloid precursor protein (APP) family. APLP2 and APP mRNA levels were increased in TGR(mRen2)27 but significantly decreased in LH rats, while only APP was increased in SHR rats.

Conclusions We report new genes associated with renin-dependent left ventricular hypertrophy. Moreover, this work shows for the first time that the APP family gene expression could be altered in response to high renin activity and this effect is independent of cardiac remodelling and hypertension.

Key Words: hypertension • cDNA array • gene expression • YWK-II • APLP2 • APP • genetically hypertensive rats • biglycan • AMPK

Journal of Renin-Angiotensin-Aldosterone System, Vol. 5, No. 2, 72-78 (2004)
DOI: 10.3317/jraas.2004.013


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