Research Profile

Synthetic grafts are used widely in vascular reconstructive surgery, but their long-term patency is less than ideal. Limited endothelial cell ingrowth contributes to long-term thrombogenicity, and smooth muscle cell accumulation and matrix deposition can progress to intimal hyperplasia and graft failure. Oxidized lipids accumulate in prosthetic grafts and contribute to cellular dysfunction.

Oxidized lipids inhibit endothelial cell migration in vitro, and the mechanisms involved are a focus of our research. Lipid oxidation products increase intracellular calcium concentration, alter cell membrane fluidity, and disrupt cytoskeletal components. Identification of the mechanisms by which oxidized lipids impair prosthetic graft healing will allow development of mechanism-based therapies to improve graft patency.

Smooth muscle cells on prosthetic grafts are characterized by a synthetic, proliferative phenotype, not the contractile phenotype of arterial smooth muscle cells. Compared with aortic smooth muscle cells, graft smooth muscle cells produce higher levels of growth factors and collagen, and these increase in response to oxidized lipids. The regulation of collagen synthesis, specifically post-transcriptional regulation of collagen secretion, is a focus of our research. A better understanding of the changes in cell function on prosthetic grafts will be used to design a better vascular graft using tissue-engineering principles.