FIBRONECTIN BIOSYNTHESIS IN ENDOTHELIAL REGENERATION AFTER INTIMAL INJURY

In this experiment, we sought to identify the major fibronectin (FN) s ynthesizing cells, the source of FN production, and the role of FN in intimal regeneration. In rats in which vascular endothelial denudation had been induced, serial morphologic changes after intimal injury wer e studied by light and electron microscopic examination using immunohi stochemical techniques and in situ hybridization. At 2 weeks after int imal injury, regenerated endothelial cells had pleomorphic cytoplasm a nd loose cellular junctions. Immunohistochemically, factor VIII-relate d antigen was localized in the regenerated endothelial cells, and immu noreaction products of FN were increased in the thickened neointima. U ltrastructurally, FN was localized in the proliferated endoplasmic ret iculum of regenerated endothelial cells in the intima, while the alpha 5 subunit of alpha 5 beta 1 integrin, one of the fibronectin receptor s, was localized in the plasma membrane and increased endoplasmic reti culum of regenerated endothelial cells. FN mRNA was localized in a lar ge number of regenerated endothelial cells (87.2 and 89.8%) by in situ hybridization at 2 and 4 weeks after intimal injury. These findings i ndicate that FN may mainly contribute to endothelial cell functions su ch as spreading and adhesion in the regenerative stage. (C) 1994 Acade mic Press, Inc.