HUMAN VENOUS ENDOTHELIUM CAN PROMOTE INTIMAL HYPERPLASIA IN A PARACRINE MANNER

Purpose: Vein graft stenoses resulting from the development of intimal hyperplasia are the major cause of graft failure in the first postoperative year. This study uses an organ culture of human saphenous vein to model vein graft intimal hyperplasia and assess the involvement of the endothelium in its development. Methods: Organ cultures of saphenous vein were established comprised of intact vein, vein denuded of endothelium, or cocultures of intact plus denuded vein for 14 days in serum-supplemented medium. At the end of the culture period, veins were processed and sections prepared for immunostaining with monoclonal alpha-smooth muscle actin, Millers elastin, QB END.10, and bromodeoxyuridine. Results: After culture, a cellular neointima developed in the intact veins that was significantly thicker than in those denuded of endothelium (24.5 vs 2.5 mu m; p = 0.0001). Denuded veins in coculture with intact veins developed a thicker neointima than did denuded veins alone (12 vs 0 mu m; p = 0.01) but less than that of intact veins (12 vs 28 mu m; p < 0.01). Proliferation indexes followed the same trend (i.e., intimal smooth muscle cell proliferation was greatest in intact and least in denuded veins). Conclusion: The endothelium can promote neointimal formation in cultured human saphenous vein through a paracrine action on the vascular smooth muscle cell.