Apoptosis of vascular smooth muscle cells (SMCs) has been described in culture and also during remodelling of the @entity1317 . However, the mediators that regulate apoptosis in SMCs are unknown. Because neurotrophins, a family of related polypeptide growth factors, including nerve growth factor (NGF) and its cognate receptor @entity2250 have been shown to be strongly expressed in @entity731 , the present study was undertaken to evaluate in vitro, the activity of NGF with regard to apoptosis of confluent cultures of @entity1 aortic SMCs. We report here that NGF induced apoptosis of SMCs in a dose-dependent manner. This effect was detected from the concentration of 1 ng/ml and reached a maximum at 100 ng/ml. The concentration that induced a half-maximum effect was 8.8 ng/ml. The pro-apoptotic activity of NGF was time dependent and was significant after 3 h of incubation. The pro-apoptotic activity of NGF was blocked in a dose-dependent manner by K-252a, an inhibitor of @entity2250 @entity669 phosphorylation, suggesting that a NGF/ @entity2250 signal transduction pathway could activate apoptotic cell death programs in @entity1 SMCs. Significantly, NGF-induced apoptosis was inhibited by @entity2307 and @entity4286 , showing that both PI3 kinase and MEK kinase were involved. At a NGF concentration that strongly induced apoptosis (100 ng/ml), @entity2533 which has been identified several times as a protective factor, dose dependently inhibited the pro-apoptotic effect of NGF. The IC50 value was 1.5 ng/ml. These results indicate that, at least in vitro, @entity2533 can inhibit the pro-apoptotic activity of NGF for SMCs therefore suggesting that @entity2533 has the capacity to diminish the deleterious consequences of an excitotoxic or @entity63 that might occur during atherogenesis or following angioplasty.

NGF exhibits a pro-apoptotic activity for @entity1 vascular smooth muscle cells that is inhibited by XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity4286 :: ('MESH:C093973', 'Chemical') :: ['PD 98059'] @entity63 :: ('MESH:D007511', 'Disease') :: ['ischemic injury'] @entity2307 :: ('MESH:C009687', 'Chemical') :: ['wortmannin'] @entity2533 :: ('7040', 'Gene') :: ['TGFbeta1'] @entity1317 :: ('MESH:D057772', 'Disease') :: ['artery following injury'] @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerotic lesions'] @entity2250 :: ('4914', 'Gene') :: ['TrkA'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine']
@entity2533 :: (7040,Gene) :: ['TGFbeta1']
