Endothelial cell behavior after denudation injury is modulated by transforming growth factor-beta1 and fibronectin

Abstract

Endothelial denudation injury after endarterectomy, autologous and synthetic grafting and balloon angioplasty leads to exposure of thrombogenic vessel wall material and may elicit an atherogenic response in the media of the affected vessels in which complete reendothelialization may not occur. While the role(s) of extracellular matrix composition and organization in this process are only incompletely understood, it is widely accepted that endothelial cells respond to matrix components in specific, complex fashions. In this report we demonstrate that large vessel endothelial cell migration is affected by the surrounding matrix and the soluble factor, transforming growth factor-beta1, which may mediate its effects, in part, by modulating endothelial cell matrix synthesis. Specifically, large vessel endothelial cell migration is decreased on a fibronectin substratum and in the presence of transforming growth factor-beta1, which increases fibronectin mRNA and protein accumulation in culture. Inhibition of sheet migration is also elicited by the addition of soluble fibronectin to the cultures. These in vitro findings are consistent with our in vivo findings of increased staining of fibronectin luminally and in the intima in the chronically deendothelialized region of a balloon catheter denuded carotid artery. Thus, reendothelialization after iatrogenic and natural injury appears to be a complex process which can be modulated by the underlying matrix and soluble factors, which may themselves modulate the matrix synthesis of local vascular cells.