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 incl uding nerve growth factor (NGF), brain-derived neurotrophic factor (BD NF and neurotrophin (NT)-3 and NT-4/5 promote the survival and differe ntiation of distinctive sets of embryonic neurons, Here we define a ne w functional role for neurotrophins, as autocrine or local paracrine m ediators of vascular smooth muscle cell migration We have identified n eurotrophins, and their cognate receptors, the trk tyrosine kinases, i n 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. Sim ilarly, rat smooth muscle cells expressed all three trk receptors as w ell as all four neurotrophins. Moreover, NGF induces cultured human sm ooth muscle cell migration at subnanomolar concentrations. In the rat aortic balloon deendothelialization model of vascular injury, the expr ession of NGF, BDNF and their receptors trk A and trk B increased dram atically 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 de monstrated in smooth muscle cells. These findings suggest that neurotr ophins play an important role lit regulating the response of vascular smooth muscle cells to injury.