Abstract 17735: Smooth Muscle Cell Specific Tsc1 Mediate Arterial Thrombosis And Arterial Injury
Background: Arterial thrombosis and arterial injury are main leading causes of cardiovascular associated death after myocardial infarction and ischemic stroke.
Methods and Results: To understand the role and mechanism of smooth muscle cell specific TSC1 in arterial thrombosis and arterial injury, we generated smooth muscle cell specific TSC1 conditional knockout mice (SMCTSC1+/-) using a conditional allele of TSC1 and a cre recombinase allele regulated by the smooth muscle protein 22 promoter. Arterial injury was induced using a left common carotid artery ligation model in heterozygous mice (SMCTSC1+/-). Arterial thrombosis and the intima and media ratios were measured at 7 and 14 days after arterial ligation. The neointimal formation was significantly increased in SMCTSC1+/- mice (intimal thickness/medial thickness ratio; 1.14 ± 0.14, p<0.001) compared with the control mice (0.13 ± 0.03). Two weeks after arterial injury, arterial thrombus area was increased in SMCTSC1+/- mice (thrombus area/luminal area ratio; 72.1 ± 4.4, p<0.001) compared with control mice (0.0 ± 0.0). Reduction of TSC1 and mammalian target of rapamycin complex 1 (mTORC1) activation including mTOR and S6 signaling pathway were observed in artery lysates of SMCTSC1+/- mice.
Conclusion: These findings suggest that arterial thrombus formation and neointimal formation using TSC1-mTORC1 mechanism might be a useful target for therapeutic intervention in arterial thrombosis and arterial injury.
- © 2013 by American Heart Association, Inc.