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

Authors: Champetier, SergeBojmehrani, AzadehBeaudoin, JonathanLachance, DominicPlante, ÉricRoussel, ÉliseCouët, JacquesArsenault, Marie
Abstract: 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.
Document Type: Article de recherche
Issue Date: 1 March 2009
Open Access Date: 14 November 2017
Document version: AM
Permalink: http://hdl.handle.net/20.500.11794/15829
This document was published in: 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
Alternative version: 10.1152/ajpheart.01046.2008
19112094
Collection:Articles publiés dans des revues avec comité de lecture

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