High molecular weight kininogen inhibition of endothelial cell function onbiomaterials

Synthetic vascular grafts implanted into humans fail to develop a complete endothelial lining. Ln previous studies, we have shown that high-molecular- weight kininogens (HMWK) adsorb to the surfaces of biomaterials. In additio n, it has been demonstrated that these proteins modulate cellular function. Ln the present study, we report on the adhesion and proliferation of human umbilical-vein endothelial cells (HUVEC) on tissue culture polystyrene, gl ass, polyurethane, and Mylar(TM) surfaces coated with human HMWK, either si ngle-chain HMWK (SC-HMWK) or double-chain HMWK (DC-HMWK). Surfaces coated w ith fibronectin served as a positive control for these experiments. Paralle l experiments were performed in which HUVEC were allowed to migrate from cr osslinked dextran microcarrier beads (Cytodex 2) onto HMWK-coated surfaces. Our results indicate that HMWK-coated surfaces inhibit endothelial cell ad hesion, proliferation, and migration at 24 and 72 h, and this inhibition is concentration dependent. To determine a potential mechanism for this inhib itory phenomenon, cells were stained for cytoskeletal actin filaments using rhodamine-phalloidin. Endothelial cells on HMWK-coated surfaces displayed F-actin filament reorganization/disassembly, characterized by the absence o f peripheral actin bands in focal adhesion contacts. We conclude that HMWK inhibit endothelial cell adhesion, proliferation, and migration on a variet y of biomaterial surfaces. This inhibitory effect may play a role in promot ing the lack of endothelialization in synthetic vascular grafts, which is t hought to play a significant role in the failure of these devices. (C) 2000 John Wiley & Sons, Inc. J Biomed Mater Res, 51, 1-9, 2000.