TGF-β Signaling in Control of Cardiovascular Function

Genetic studies in animals and humans indicate that gene mutations that functionally perturb transforming growth factor beta (TGF-beta) signaling are linked to specific hereditary vascular syndromes, including Osler-Rendu-Weber disease or hereditary hemorrhagic telangiectasia and Marfan syndrome. Disturbed TGF-beta signaling can also cause nonhereditary disorders like atherosclerosis and cardiac fibrosis. Accordingly, cell culture studies using endothelial cells or smooth muscle cells (SMCs), cultured alone or together in two-or three-dimensional cell culture assays, on plastic or embedded in matrix, have shown that TGF-beta has a pivotal effect on endothelial and SMC proliferation, differentiation, migration, tube formation, and sprouting. Moreover, TGF-beta can stimulate endothelial-to-mesenchymal transition, a process shown to be of key importance in heart valve cushion formation and in various pathological vascular processes. Here, we discuss the roles of TGF-beta in vasculogenesis, angiogenesis, and lymphangiogenesis and the deregulation of TGF-beta signaling in cardiovascular diseases.