Regulation of endothelial cell growth, architecture, and matrix synthesis by TGF-beta.

Transforming growth factor-beta (TGF-beta) has profound effects on all cell types making up the vasculature, including endothelial cells, smooth muscle cells, and adventitial connective tissue. As such, it plays a prominent role not only in the physiologic vasculogenesis and angiogenesis characteristic of embryogenesis and inflammation and repair but also in vascular disorders such as the arterial thickening associated with pulmonary hypertension. The actions of TGF-beta on these vascular cells in vitro and in vivo are extremely complex. In vitro, TGF-beta inhibits both the proliferation and migration of endothelial cells in monolayer culture, but it promotes organization of the cells into tubelike structures in three-dimensional culture in collagen gels. TGF-beta also increases synthesis of fibronectin and decreases secretion of proteases by both endothelial cells and fibroblasts; the resultant changes in matrix composition could mediate the effects of TGF-beta on both the growth and phenotype of these cells, and overexpression could contribute to fibrosis. TGF-beta also regulates the synthesis by endothelial cells of platelet-derived growth factor, which can stimulate growth of vascular smooth muscle cells. In vivo, TGF-beta stimulates neovascularization at local sites of injection and also is angiogenic when assayed in the rabbit cornea or on the chick chorioallantoic membrane. However, because angiogenesis involves the participation of many different cell types, effects of TGF-beta on inflammatory cells must also be considered. Thus, the ability of TGF-beta to chemoattractant macrophages and to increase expression by the cells of mRNAs for several growth factors known to act on endothelial cells, smooth muscle cells, and fibroblasts must also be considered.