Enhanced Cellular Proliferation in Intact Stenotic Lesions Derived From Human Arteriovenous Fistulas and Peripheral Bypass Grafts

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Abstract
Background Vascular interventions are often complicated by the development of intimal thickening, leading to stenosis. Cellular proliferation is a key event in stenosis formation in animals, but the role of cell proliferation in intimal thickening in humans is still unclear. Furthermore, the relation between proliferation in human stenotic lesions and flow parameters has not been established. Methods and Results We studied the proliferation patterns of 35 anatomically intact human stenotic lesions derived from either peripheral bypasses (normal flow) or hemodialysis AV fistulas (high flow) with the use of Ki-67, a cell proliferation marker. Local flow parameters were assessed with ultrasound. Proliferation patterns were similar in AV fistula and bypass stenoses. In the intima, proliferation was highest in the area just below the endothelium (AV fistulas, 3.6%; bypasses, 3.5%; P =NS). In adjacent nonstenotic vessel segments that were used as controls, proliferation rate in the intima was 0.3%. Double-labeling studies revealed that subendothelial-intimal proliferation consisted mainly (90%) of vascular smooth muscle cells, whereas proliferation in the other layers of the vessel wall also consisted of endothelial cells and macrophages. Blood flow velocity was negatively correlated with subendothelial-intimal proliferation ( r =−.61, P <.05). The endothelial cell coverage of the lumen was positively correlated with proliferation ( r =.85, P <.01). Conclusions These data suggest enhanced cellular proliferation in human stenotic tissue derived from AV fistulas and peripheral bypass grafts. Furthermore, high proliferation rates seem to be associated with endothelial cell coverage of the lumen and low local flow velocities.