INTERSTITIAL-CELLS FROM THE ATRIAL AND VENTRICULAR SIDES OF THE BOVINE MITRAL-VALVE RESPOND DIFFERENTLY TO DENUDING ENDOCARDIAL INJURY

The mitral valve has atrial and ventricular sides, each lined by endoc ardial cells. The valve stroma contains alpha smooth muscle actin posi tive interstitial cells, collagen, glycosaminoglycans, and elastic tis sue. To eliminate the effect of endocardium on wound repair in bovine mitral valve organ culture, the endocardium was removed from both side s of the valve. At 6 days, organ cultures of these preparations reveal ed surface cells on the ventricular side but not on the atrial side. V entricular surface cells were negative for Factor VIII-related antigen , and positive for a smooth muscle actin. Immuno-peroxidase staining f or proliferating cell nuclear antigen/cyclin, a marker for cell prolif eration, revealed a positive labeling index of (mean +/- standard devi ation) 0.08 +/- 0.16% for interstitial cells from the atrial side and 0.14 +/- 0.19% for ventricular side interstitial cells in uncultured p reparations (not significant), and 0.44 +/- 0.69% for atrial side inte rstitial cells and 2.25 +/- 1.64% for ventricular side interstitial ce lls in the cultured preparations (significant, P < 0.0006). The result s suggest that in organ culture, interstitial cells from the ventricul ar side of the mitral valve respond to a denuding endocardial injury b y proliferating and migrating onto the adjacent surface whereas inters titial cells from the atrial side do not. This difference in the respo nse to injury of interstitial cells from the atrial and ventricular si des of the valve may reflect differences in phenotype or may be due to effects of extracellular matrix on interstitial cell behavior. The la tter is possible because of differences in the extracellular matrix of the atrial and ventricular sides of the valve.