FUNCTIONAL COUPLING OF VALVULAR INTERSTITIAL CELLS AND COLLAGEN VIA α₂β₁ INTEGRINS IN THE MITRAL LEAFLET

Once considered passive flaps, we now understand that mitral leaflets are dynamic structures with their own vasculature and innervation that actively remodel and even generate force in response to their environments. Valvular interstitial cells (VICs) are contractile and could underlie mitral leaflet force generation, but the exact mechanisms for VICs in mitral leaflet force generation are not understood. This study tested the hypothesis that actin-mediated VIC force generation coupled to collagen via alpha₂beta₁ integrins is necessary for force generation in the mitral leaflet. High magnification fluorescent imaging of freshly excised porcine mitral leaflets revealed VIC cytoplasm tightly conforming to collagen fibers, with actin within VIC cytoplasmic processes appearing to attach to the collagen fibers. Functional studies of isometric force development demonstrated that while control samples developed force in response to KCl, either blocking alpha₂beta₁ integrins or blocking actin polymerization via cytochalasin abolished KCl-induced force development (p<0.001). These results strongly suggest that VIC-collagen coupling, mediated by alpha₂beta₁ integrins, is necessary for KCl-induced force generation in the mitral leaflet. This functional coupling between collagen and VICs via alpha₂beta₁ integrins may play a role for in vivo mitral valve function.