Endothelial control of vascular smooth muscle proliferation in an organ culture of human saphenous vein.

Abstract

We have investigated the positive and negative regulation of vascular smooth muscle cell (VSMC) proliferation by proposed endothelium-derived mediators using organ cultures of freshly isolated and surgically prepared human saphenous vein. We observed that: (1) whereas platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) are known to stimulate proliferation, agents that minic the action of prostacyclin and nitric oxide (NO), inhibit proliferation; (2) the production of PDGF, bFGF, prostacyclin and NO are endothelium-dependent in veins before culture--PDGF production is induced in VSMC during intima formation; (3) removal of endothelium has a net inhibitory effect on intimal VSMC proliferation; (4) antibodies to bFGF reduced intimal VSMC proliferation in surgically prepared veins. Hence, in this preparation, PDGF, bFGF, prostacyclin and NO are all possible endothelium-dependent regulators of VSMC proliferation. Use of selective inhibitors (as exemplified here by antibodies to bFGF) and reconstitution of endothelium in the organ culture model promise to be valuable to test the roles of these mediators further.