Smooth muscle cell proliferation in response to injury in an organ culture of human saphenous vein

Abstract

The principal cause of late vein graft occlusion is intimal smooth muscle cell proliferation, the underlying basis of which remains an enigma. Early theories implicating platelet activation now appear untenable since intimal proliferation progresses after endothelial repair, and is little influenced by antithrombotic treatments. We developed an organ culture of human saphenous vein to investigate the basis of intimal proliferation in a preparation which preserved the anatomical relationships of endothelium, smooth muscle and extracellular matrix. Tissue viability remained high during culture for up to 14 days and intimal smooth muscle proliferation occurred. The removal of endothelium reduced intimal thickening in cultured veins from 26 +/- 5 to 6 +/- 3 microns and also reduced the number of intimal cells/mm labelled with [3H]-thymidine from 12 +/- 4 to 3 +/- 1 (both p less than 0.01, n = 10). Surgical preparation of vein resulted in significant injury to medial smooth muscle cells, which was only partially reversed during culturing. Surgical preparation did not affect intimal proliferation, but stimulated medial proliferation from 3 +/- 1 to 32 +/- 9 [3H]-thymidine-labelled cells/mm (p less than 0.01, n = 11). These experiments reveal evidence for proliferation enhancing factors derived from endothelium and injured smooth muscle cells, which probably participate in intimal proliferation in vein grafts. Inhibiting their action may therefore present new possibilities for therapy.