ENHANCED CELLULAR PROLIFERATION IN INTACT STENOTIC LESIONS DERIVED FROM HUMAN ARTERIOVENOUS-FISTULAS AND PERIPHERAL BYPASS GRAFTS - DOES ITCORRELATE WITH FLOW PARAMETERS

Background Vascular interventions are often complicated by the develop ment of intimal thickening, leading to stenosis. Cellular proliferatio n is a key event in stenosis formation in animals, but the role of cel l proliferation in intimal thickening in humans is still unclear. Furt hermore, the relation between proliferation in human stenotic lesions and flow parameters has not been established. Methods and Results We s tudied the proliferation patterns of 35 anatomically intact human sten otic lesions derived from either peripheral bypasses (normal flow) or hemodialysis AV fistulas (high flow) with the use of Ki-67, a cell pro liferation marker. Local flow parameters were assessed with ultrasound . Proliferation patterns were similar in AV fistula and bypass stenose s. In the intima, proliferation was highest in the area just below the endothelium (AV fistulas, 3.6%; bypasses, 3.5%; P=NS). In adjacent no nstenotic vessel segments that were used as controls, proliferation ra te in the intima was 0.3%. Double-labeling studies revealed that suben dothelial-intimal proliferation consisted mainly (90%) of vascular smo oth muscle cells, whereas proliferation in the other layers of the ves sel wall also consisted of endothelial cells and macrophages. Blood fl ow velocity was negatively correlated with subendothelial-intimal prol iferation (r=-.61, P<.05). The endothelial cell coverage of the lumen was positively correlated with proliferation (r=.85, P<.01). Conclusio ns These data suggest enhanced cellular proliferation in human stenoti c tissue derived from AV fistulas and peripheral bypass grafts. Furthe rmore, high proliferation rates seem to be associated with endothelial cell coverage of the lumen and low local how velocities.