BACKGROUND: Restenosis is a major complication that limits the long-term efficacy of coronary angioplasty. Migration and proliferation of activated medial smooth muscle cells (SMCs) is considered an important mechanism in this process. Because at sites of @entity1317 , aggregating platelets release both @entity750 ( @entity750 ) and @entity2404 ( @entity3447 ), we examined whether @entity750 and @entity3447 can induce SMC proliferation and whether there is synergistic interaction between these two mediators. METHODS AND RESULTS: The mitogenic effects of @entity750 and @entity3447 either alone or in combination was examined in serum-free medium on @entity235 aortic SMCs by @entity665 incorporation into DNA and by cell counting. @entity750 induced SMC proliferation at a concentration of 100 nmol/L, whereas the effect of @entity3447 ( @entity2872 , a stable @entity3447 mimetic) on inducing proliferation of SMCs was observed at a concentration of 100 nmol/L. When these two mediators were added together, there was a synergistic interaction on inducing SMC proliferation even at subthreshold concentrations. The mitogenic effect of @entity750 and its synergistic interaction with @entity3447 on SMC proliferation was abolished by a 5-HT2 receptor antagonist, @entity69839 , without affecting the contribution of @entity3447 . Similarly, the @entity3447 synthase inhibitor/receptor antagonist @entity18648 abolished the mitogenic effect of @entity3447 and the interaction between @entity750 and @entity3447 without affecting the response to @entity750 . When @entity69839 and @entity18648 were used together, they abolished the mitogenic effects of @entity750 and @entity3447 . CONCLUSIONS: At sites of @entity1317 , platelet-induced SMC proliferation may also be modulated by nonpeptide growth mediators. A combination of a 5-HT2 receptor antagonist and @entity3447 synthase inhibitor/receptor may be useful for attenuation of restenosis after angioplasty.

Effect of XXXX , @entity2404 , and specific receptor antagonists on vascular smooth muscle cell proliferation.

@entity18648 :: ('MESH:C060219', 'Chemical') :: ['ridogrel'] @entity3447 :: ('CHEBI:15627', 'Chemical') :: ['TXA2'] @entity235 :: ('9615', 'Species') :: ['canine'] @entity2404 :: ('MESH:D013928', 'Chemical') :: ['thromboxane A2'] @entity69839 :: ('MESH:C054583', 'Chemical') :: ['LY281067'] @entity2872 :: ('MESH:D019796', 'Chemical') :: ['U46619'] @entity665 :: ('CHEBI:53526', 'Chemical') :: ['[3H]thymidine'] @entity750 :: ('MESH:D012701', 'Chemical') :: ['serotonin', '5-HT'] @entity1317 :: ('MESH:D057772', 'Disease') :: ['vascular injury']
@entity750 :: (MESH:D012701,Chemical) :: ['serotonin']
