Progression and regression of myointimal hyperplasia in experimental vein grafts depends on platelet-derived growth factor and basic fibroblastic growth factor production

Abstract

The factors that lead to myointimal hyperplasia (MH) in arterial vein grafts (AVGs) are unknown. Platelet-derived growth factor (PDGF) and basic fibroblastic growth factor (bFGF) are two powerful mitogens for smooth muscle cells that have been implicated in the genesis of MH. The aim of this study was to analyze the correlation between progression and regression of MH and production of PDGF and bFGF in experimental vein grafts. In 64 inbred Lewis rats, a 1-cm segment of inferior vena cava was inserted at the level of the abdominal aorta. The segments of inferior vena cava were obtained from syngenic rats. In 48 rats, the AVG was explanted 3 days (n = 8), 7 days (n = 8), 4 weeks (n = 24), and 12 weeks (n = 8) after surgery. In 16 rats the vein graft was explanted after being in the arterial system for 4 weeks and was reimplanted as a venous-venous bypass in syngenic Lewis rats. Reimplanted vein grafts (RVGs) were explanted 2 weeks (n = 8) and 8 weeks (n = 8) later. Grafts were analyzed by light and electron microscopy, morphometry, and histochemistry, and were put in organ culture to assess PDGF and bFGF production and mitogenic activity. We observed MH formation in AVGs and MH regression in RVGs (p < 0.001).PDGF and bFGF production correlated with the degree of MH (p < 0.01). Histochemistry showed PDGF and bFGF in the area of MH in AVG, which disappeared in RVG. Conditioned media from AVG had greater mitogenic activity than RVG or control veins. MH formation and regression in experimental vein grafts correlate with PDGF and bFGF production.