In an ovine model, ischaemic mitral regurgitation induced significant permanent plastic radial deformation of the mitral valve leaflet and transient transcriptomic changes without collagen damage.
What are the multiscale mechanisms of mitral valve leaflet remodeling following myocardial infarction in an ovine model?
In an ovine model, ischaemic mitral regurgitation induces plastic deformation of the mitral valve and transient transcriptomic changes without functional damage to collagen fibres.
Ischaemic mitral regurgitation (IMR), a frequent complication following myocardial infarction (MI), leads to higher mortality and poor clinical prognosis if untreated. Accumulating evidence suggests that mitral valve (MV) leaflets actively remodel post MI, and this remodelling increases both the severity of IMR and the occurrence of MV repair failures. However, the mechanisms of extracellular matrix maintenance and modulation by MV interstitial cells (MVICs) and their impact on MV leaflet tissue integrity and repair failure remain largely unknown. Herein, we sought to elucidate the multiscale behaviour of IMR-induced MV remodelling using an established ovine model. Leaflet tissue at eight weeks post MI exhibited significant permanent plastic radial deformation, eliminating mechanical anisotropy, accompanied by altered leaflet composition. Interestingly, no changes in effective collagen fibre modulus were observed, with MVICs slightly rounder, at eight weeks post MI. RNA sequencing indicated that YAP-induced genes were elevated at four weeks post MI, indicating elevated mechanotransduction. Genes related to extracellular matrix organization were downregulated at four weeks post MI when IMR occurred. Transcriptomic changes returned to baseline by eight weeks post MI. This multiscale study suggests that IMR induces plastic deformation of the MV with no functional damage to the collagen fibres, providing crucial information for computational simulations of the MV in IMR.
Howsmon et al. (Fri,) conducted a other in Ischaemic mitral regurgitation post myocardial infarction. Ischaemic mitral regurgitation (IMR) vs. Baseline was evaluated on Mitral valve leaflet remodelling (plastic radial deformation, mechanical anisotropy, gene expression). In an ovine model, ischaemic mitral regurgitation induced significant permanent plastic radial deformation of the mitral valve leaflet and transient transcriptomic changes without collagen damage.