NEUROTROPHIN AND NEUROTROPHIN RECEPTORS IN VASCULAR SMOOTH-MUSCLE CELLS - REGULATION OF EXPRESSION IN RESPONSE TO INJURY

The neurotrophins, a family of related polypeptide growth factors including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF and neurotrophin (NT)-3 and NT-4/5 promote the survival and differentiation of distinctive sets of embryonic neurons, Here we define a new functional role for neurotrophins, as autocrine or local paracrine mediators of vascular smooth muscle cell migration We have identified neurotrophins, and their cognate receptors, the trk tyrosine kinases, in human and mt vascular smooth muscle cells in viva In vitro cultured human smooth muscle cells express BDNF; NT-3; and trk A, B, and C. Similarly, rat smooth muscle cells expressed all three trk receptors as well as all four neurotrophins. Moreover, NGF induces cultured human smooth muscle cell migration at subnanomolar concentrations. In the rat aortic balloon deendothelialization model of vascular injury, the expression of NGF, BDNF and their receptors trk A and trk B increased dramatically in the area of injury within 3 days and persisted during the formation of the neointima. lit human coronary atherosclerotic lesions, BDNF NT-3, and NT-4/5, and the trk B and trk C receptors could be demonstrated in smooth muscle cells. These findings suggest that neurotrophins play an important role lit regulating the response of vascular smooth muscle cells to injury.