Agrandissement des feuillets mitraux en insuffisance aortique : un mécanisme actif pouvant prévenir l'insuffisance mitrale dans le ventricule dilaté
|Advisor:||Beaudoin, Jonathan; Couët, Jacques|
|Abstract:||Mitral leaflet enlargement in patients with chronic aortic regurgitation (AR) has been recently identified as an adaptive mechanism to prevent functional mitral regurgitation (FMR) in dilated left ventricles (LV). The timing of these morphologic changes is not known, and it is not clear if leaflet expansion is the result of active growth vs passive valve stretching. We hypothesised that pathways of growth are activated early in response to AR. We used a rat model of AR (retrograde aortic perforation) known to cause initial rapid LV dilatation (first 2 months), followed by a chronic phase with slower LV remodeling. AR was induced in 58 rats vs 53 sham. Animals were euthanized at different time points after AR creation (48 hours, 1 week and 3 months). AR severity, FMR and LV dilatation were assessed by serial echocardiograms. Mitral valves were harvested for microscopic and molecular analyses to document reactivation of embryonic growth pathways. AR animals had increased LV dimension and mitral annulus size. No animal developed FMR. No change in leaflet length or thickness was seen at 48h, however anterior mitral leaflets were longer in AR animals at 1 week and 3 months. By microscopy, mitral leaflets in AR animals were thicker at 1 week and 3 months. Molecular changes were present early (48 hours and one week) suggesting active matrix remodeling. RT-PCR studies showed increased collagen, α-sma, TGF-β1 and MMP-2 expression in the leaflets at 1 week. At 3 months, these molecular changes were not seen. This model of AR with progressive LV dilatation induces active expansion and thickening of the mitral leaflets. Growth signals are seen acutely but not at 3 months suggesting that most of this enlargement occurs early and in parallel of LV dilatation. Stimulation of this growth could represent a new strategy to prevent FMR in patients with dilated LV.|
|Document Type:||Mémoire de maîtrise|
|Open Access Date:||24 April 2018|
|Collection:||Thèses et mémoires|
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