Gene profiling of left ventricle eccentric hypertrophy in aortic regurgitation in rats : rationale for targeting the β-adrenergic and renin-angiotensin systems

Auteur(s): Champetier, SergeBojmehrani, AzadehBeaudoin, JonathanLachance, DominicPlante, ÉricRoussel, ÉliseCouët, JacquesArsenault, Marie
Autre(s) titre(s): Gene profiling in volume-overload LV hypertrophy
Résumé: Aortic valve regurgitation (AR) imposes a severe volume overload to the left ventricle (LV), which results in dilation, eccentric hypertrophy, and eventually loss of function. Little is known about the impact of AR on LV gene expression. We, therefore, conducted a gene expression profiling study in the LV of rats with acute and severe AR. We identified 64 genes that were specifically upregulated and 29 that were downregulated out of 21,910 genes after 2 wk. Of the upregulated genes, a good proportion was related to the extracellular matrix. We subsequently studied a subset of 19 genes by quantitative RT-PCR (qRT-PCR) to see if the modulation seen in the LV after 2 wk persisted in the chronic phase (after 6 and 12 mo) and found that it did persist. Knowing that the adrenergic and renin-angiotensin systems are overactivated in our animal model, we were interested to see if blocking those systems using metoprolol (25 mg·kg−1·day−1) and captopril (100 mg·kg−1·day−1) would alter the expression of some upregulated LV genes in AR rats after 6 mo. By qRT-PCR, we observed that upregulations of LV mRNA levels encoding for procollagens type I and III, fibronectin, atrial natriuretic peptide, transforming growth factor-β2, and connective tissue growth factor were totally or partially reversed by this treatment. These observations provide a molecular rationale for a medical strategy aiming these systems in the medical treatment of AR and expand the paradigm in the study of this form of LV volume overload.
Type de document: Article de recherche
Date de publication: 1 mars 2009
Date de la mise en libre accès: 14 novembre 2017
Version du document: AM
Lien permanent: http://hdl.handle.net/20.500.11794/15829
Ce document a été publié dans: American journal of physiology. Heart and circulatory physiology, Vol. 296 (3), H669-H677 (2009)
https://doi.org/10.1152/ajpheart.01046.2008
American Physiological Society
Autre version disponible: 10.1152/ajpheart.01046.2008
19112094
Collection :Articles publiés dans des revues avec comité de lecture

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