Growth factor gene expression by intimal cells in healing polytetrafluoroethylene grafts

Abstract

Vascular smooth muscle cell proliferation resulting in intimal hyperplasia is a major cause of late graft failure. In baboons, healing 60 μm internodal distance polytetrafluoroethylene vascular grafts form an intima composed of proliferating smooth muscle cells with a luminal lining of endothelium. The presence of intimal smooth muscle cell proliferation underneath an intact endothelium, without platelet adherence, suggests that intimal cells rather than platelets may provide the growth factors regulating the smooth muscle cell proliferation. This idea is supported by the observation that, when segments of graft and artery are excised and perfused ex vivo, there is greater mitogenic activity present in the graft perfusate compared to artery perfusate. Two factors expressed by vascular wall cells and known to influence smooth muscle cell growth in vitro are platelet-derived growth factor and transforming growth factor-β1. The expression of these growth factors was measured by Northern blot analysis of total ribonucleic acid extracted from thoracic aorta and the intima of 6-week thoracoabdominal polytetrafluoroethylene grafts, and from smooth muscle cell cultured from the aorta and polytetrafluoroethylene graft. Growth of the cultured smooth muscle cell was arrested in serum-free conditions for 3 days and then stimulated with 10% fetal calf serum. Twenty-four hours later, the smooth muscle cells were harvested. Probing the blots for platelet-derived growth factor-A, platelet-derived growth factor-B, and transforming growth factor-β1 messenger ribonucleic acid revealed that in vivo, the graft intima expressed more platelet-derived growth factor-A than the aorta. Both tissues expressed very low levels of platelet-derived growth factor-B, and they both expressed variable levels of transforming growth factor-β1. In vitro, smooth muscle cell from both graft intima and aorta had the capacity to express platelet-derived growth factor-A, platelet-derived growth factor-B, and transforming growth factor-β1 messenger ribonucleic acid. These findings support the concept that the intimal cells express known growth factor genes and that smooth muscle cell proliferation observed in healing grafts may be regulated by factors from the cells within the vessel wall rather than from platelets.