Interstitial cells from the atrial and ventricular sides of the bovine mitral valve respond differently to denuding endocardial injury

Summary The mitral valve has atrial and ventricular sides, each lined by endocardial cells. The valve stroma contains α smooth muscle actin positive interstitial cells, collagen, glycosaminoglycans, and elastic tissue. To eliminate the effect of endocardium on wound repair in bovine mitral valve organ culture, the endocardium was removed from both sides of the valve. At 6 days, organ cultures of these preparations revealed surface cells on the ventricular side but not on the atrial side. Ventricular surface cells were negative for Factor VIII-related antigen, and positive for α smooth muscle actin. Immuno-peroxidase staining for proliferating cell nuclear antigen/cyclin, a marker for cell proliferation, revealed a positive labeling index of (mean ± standard deviation) 0.08 ± 0.16% for interstitial cells from the atrial side and 0.14 ± 0.19% for ventricular side interstitial cells in uncultured preparations (not significant), and 0.44 ± 0.69% for atrial side interstitial cells and 2.25 ± 1.64% for ventricular side interstitial cells in the cultured preparations (significant,P<0.0006). The results suggest that in organ culture, interstitial cells from the ventricular side of the mitral valve respond to a denuding endocardial injury by proliferating and migrating onto the adjacent surface whereas interstitial cells from the atrial side do not. This difference in the response to injury of interstitial cells from the atrial and ventricular sides of the valve may reflect differences in phenotype or may be due to effects of extracellular matrix on interstitial cell behavior. The latter is possible because of differences in the extracellular matrix of the atrial and ventricular sides of the valve.