PMC

H&E staining of the native (A-C) and decellularized (D-F) mitral valve chordae (A and D), aortic valve leaflet (B and E) and mitral valve leaflet (C and F) ECMs. Mavot’s pentachrome staining of the decellularized mitral valve chordae (G), aortic valve leaflet (H), and mitral valve leaflet (I) ECMs. SEM images of the decellularized mitral valve chordae (J), aortic valve leaflet (K) and mitral valve leaflet (L) ECMs. Macroscopic images to show the native morphologies of mitral valve chordae (M), aortic valve leaflet (N) and mitral valve leaflet (O) isolated from a porcine heart.

Angiograms before and after Melody valve deployment in a patient with a failing Sorin Mitroflow bioprosthetic valve (inset). Panel A shows free pulmonary insufficiency and stenosis due to calcification of the leaflets of the bioprosthetic valve. Panel B shows the Melody valve seated in the bioprosthetic valve. There is no residual pulmonary insufficiency or stenosis.

A, Diagram showing the role of Nfatc1 in defining valve mesenchymal interaction during semilunar valve morphogenesis. In E11.5 Nfatc1^+/+ embryos, apposition of endocardium-derived mesenchyme from EMT at pOFT (blue cells) and cardiac neural crest–derived mesenchyme from migration at dOFT (green cells) establishes a mesenchymal tissue boundary for semilunar valve formation. From E11.5 to E12.5, the valve elongates from the boundary and becomes primitive valve leaflets. In Nfatc1^−/− embryos, this tissue boundary is shifted into the dOFT because of an increased endocardium-derived mesenchyme from augmented EMT in the pOFT and subsequently decreased neural crest–derived mesenchyme in the dOFT. The alteration of heterogeneous mesenchymal tissue populations (and reduced valve endocardial proliferation not shown in the model) disrupts post-EMT valve elongation. B, A simple diagram shows that Nfatc1 transcriptionally regulates EMT and valve endocardial cell proliferation. Nfatc1 maintains an endocardial cell phenotype through suppression of expression of Snail1 and Sanil2, thereby maintaining the VE-Cad expression necessary for a tight cell-cell contact of the valve endocardial cells that prevents them from undergoing EMT. Nfatc1 also positively regulates the proliferation of valve endocardial cells necessary for the growth of valve leaflets mediated by unknown factors.

Relative frequency distribution of (A) ethiopathogeny and (B) cardiac operations by procedure type. AVR=aortic valve replacement; AVR+CABG=aortic valve replacement associated with coronary artery bypass surgery; AVR+MVRr=aortic valve replacement with mitral valve replacement or repair; MVr=mitral valve repair; MVr+CABG=mitral valve repair associated with coronary artery bypass surgery; MVR=mitral valve replacement; MVR+CABG=mitral valve replacement associated with coronary artery bypass surgery; MVRr+TVr=mitral valve replacement or repair associated with tricuspid valve repair; Others=other surgeries (including pulmonary valve surgery, aortic valve replacement associated with tricuspid valve repair and isolated tricuspid valve surgery).