Characterization of Molecules Mediating Cell-Cell Communication in Human Cardiac Valve Interstitial Cells

Abstract

Cell-cell interactions and adhesion determine cellular architectural organization, proliferation, signaling, differentiation, and death. We have identified the molecular components of different cell-cell junctions in human valve interstitial cells (ICs) both in situ and in culture. ICs were isolated, cultured, and phenotyped for cell surface and cytoplasmic markers by flow cytometry and immunocytochemistry. Western blotting was used to identify and quantify the molecular components of these cell-cell junctions in human valve ICs and compared with expression in smooth muscle and fibroblast cell types. N-cadherin and desmoglein were weakly detected on a low percentage of ICs, and the other classical cadherins were not detected. alpha- and beta-catenin, but not gamma-catenin, were expressed at equivalent levels by all valve ICs. Valve ICs did not express connexin-32 and -40; however, connexin-26 and -43 were equally expressed by a low percentage of ICs, demonstrating cell surface and cytoplasmic expression ,and connexin-45 was weakly expressed. The other cell types also expressed N-cadherin, alpha- and beta-catenin, desmoglein and connexin-43. The expression of these junctional molecules was predominantly by valve ICs on the inflow side of the valves. Human valve ICs have the ability to communicate with other valve ICs and mediate cell-cell adhesion via N-cadherin, connexin-26 and -43, and desmoglein. The junctions between valve ICs could support an interconnecting and coordinated cellular unit capable of controlling the functionality of the valve.