Dual Role of VEGF in Pretreated Experimental ePTFE Arterial Grafts

Abstract

Lack of endothelialization and abnormal smooth muscle cell (SMC) growth adversely affect the outcome of vascular synthetic grafts. The aims of our study were to investigate how a coating of extracellular matrix (ECM) and vascular endothelial growth factor (VEGF) might affect the endothelialization rate, smooth muscle cells (SMC) proliferation, and myointimal hyperplasia in experimental arterial ePTFE grafts. In each of 30 male Lewis rats, a 1-cm-long ePTFE graft was inserted at the level of the abdominal aorta. Animals were randomized in five groups (six animals each): groups A and A1 received ePTFE grafts coated with a synthetic extracellular matrix (growth factor-reduced matrigel) containing VEGF; groups B and B1 received ePTFE grafts coated with synthetic ECM; and group C received ePTFE grafts alone. The grafts were explanted at 30 days from surgery for immunohistochemical analysis. Both endothelialization rate and myointimal hyperplasia were augmented in group A versus groups B and C, and these findings were statistically significant. SMC density resulted significantly higher in group A versus groups B and C, and this was associated with an altered expression of bFGF and TGFbeta. Pretreating ePTFE grafts with synthetic ECM and VEGF results in better endothelialization, but also in undesired higher SMC density and myointimal hyperplasia.