Increased platelet-derived growth factor production and intimal thickening during healing of Dacron grafts in a canine model

Abstract

Purpose: Growth factor production by endothelial cells on grafts may play a role in the development of intimal hyperplasia and subsequent graft failure.Methods: To study the relationship between platelet-derived growth factor production and graft healing, 26 beagles underwent placement of 20 cm long, 6 mm internal diameter, knitted Dacron thoracoabdominal grafts, either seeded with autologous endothelial cells (n = 14) or unseeded controls (n = 12). The grafts and adjacent arteries were removed 4 or 20 weeks after implantation for measurement of platelet-derived growth factor production in organ culture, endothelial cell coverage, and intimal thickness.Results: Midgraft platelet-derived growth factor production by seeded graft segments increased from 41 ± 6 to 148 ± 27 pg/cm2/72 hr (p < 0.002) between 4 and 20 weeks. This was accompanied by a significant increase in inner-capsule thickness. Platelet-derived growth factor production by control graft segments also increased from 58 ± 21 to 163 ± 42 pg (p < 0.05) and was similar to that of seeded grafts despite more rapid endothelialization of seeded grafts. The increase in growth factor production by Dacron grafts was greater than that of the expanded polytetrafluoroethylene grafts studied previously despite similar endothelial cell coverage.Conclusion: This increase corresponded with the rapid appearance of smooth muscle cells in the pseudointima of Dacron grafts, suggesting that these cells may be responsible for the observed increase in platelet-derived growth factor production.