INTERACTION OF ENDOTHELIAL-CELLS AND FIBROBLASTS WITH MODIFIED FIBRINNETWORKS - ROLE IN ATHEROSCLEROSIS

Fibrinogen has been recognised in recent years as an independent risk factor in athero/thrombogenesis. However, the mechanism by which eleva ted fibrinogen translates into higher incidence of atherosclerosis is not known. One possible mechanism may be through the modification of f ibrin. While it is already known that fibrin network is altered in dis ease states like peripheral vascular disease, diabetes, hypercholester olaemia and myocardial infarction, the influence of altered fibrin net work structure on growth and function of endothelial cells (EC) and fi broblasts (FB) requires investigation. Fibrin network structure in pla sma clots was modified by changing pH and characterised using establis hed biophysical methods. PGI(2), von Willebrand Factor (vWF), t-PA and PAI-1 were measured to evaluate changes in cell function induced by m odified fibrin structure. In general, networks composed of thin fibres induced growth over their entire layer. Networks composed of thick fi bres and open matrix promoted infiltration of cells into gel matrix an d growth of macrovascular structures. Furthermore, thin fibres promote d a more prothrombotic environment as observed from changes in cell bi ochemical function. Fibrin, whilst initially acting as a scaffolding f or cellular and biochemical processes, may also alter cell function an d determine the progress of atherosclerosis. (C) 1997 Elsevier Science Ireland Ltd.