Fibronectin biosynthesis in endothelial regeneration after intimal injury

In this experiment, we sought to identify the major fibronectin (FN) synthesizing 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 were studied by light and electron microscopic examination using immunohistochemical techniques and in situ hybridization. At 2 weeks after intimal injury, regenerated endothelial cells had pleomorphic cytoplasm and loose cellular junctions. Immunohistochemically, factor VIII-related antigen was localized in the regenerated endothelial cells, and immunoreaction products of FN were increased in the thickened neointima. Ultrastructurally, FN was localized in the proliferated endoplasmic reticulum of regenerated endothelial cells in the intima, while the alpha 5 subunit of alpha 5 beta 1 integrin, one of the fibronectin receptors, was localized in the plasma membrane and increased endoplasmic reticulum of regenerated endothelial cells. FN mRNA was localized in a large number of regenerated endothelial cells (87.2 and 89.8%) by in situ hybridization at 2 and 4 weeks after intimal injury. These findings indicate that FN may mainly contribute to endothelial cell functions such as spreading and adhesion in the regenerative stage.