The role of cell proliferation and migration in the development of a neo-intimal layer in veins grafted into arteries, in rats

Abstract

The development of a thickened (hyperplastic) fibro-cellular neo-intima is a significant event in the adaptation of a vein grafted into an artery. The histogenesis of tissues in vein grafts was explored in a rat model where the source of endothelial and smooth muscle cells was from the adjacent artery. Cell proliferation was assessed by the incorporation of tritiated thymidine and autoradiography, up to 18 months after grafting. Cell migration was detected by prelabelling in the first 5 days after grafting and sampling at later times. The proliferation of cells in the arterial media adjacent to the graft was elevated above control levels as early as 2 days after grafting; it was maximal at 3 days and returned to low levels by day 21. During the first week, prelabelled smooth muscle cells in the tunica media of the adjacent artery migrated to the subendothelial space, where they continued to proliferate to produce arterial intimal hyperplasia. The migration of endothelial and smooth muscle cells proceeded across the anastomosis to populate the vein graft neo-intima, where smooth muscle cells continued to proliferate until 28 days after grafting. Cell migration and proliferation were significant factors in the histogenesis of vein graft neo-intimal hyperplasia in this model. These processes were controlled, perhaps by local regulatory factors, to form a vein graft, the wall of which was similar in thickness and structure to that of the host artery.