Abstract 19695: Platelet TSC1 is an Important Mediator of Arterial Thrombosis
Background: Arterial thrombosis is responsible for peripheral vascular disease, myocardial infarction, and stroke. Mammalian target of rapamycin (mTOR) inhibition promotes arterial thrombosis. To determine the contributions of platelet specific Tuberous sclerosis 1 (TSC1) deficiency to arterial thrombosis, we generated PF4Cre-TSC1flox/+ mice. Because the effect of mTOR activation on thrombus formation in vivo has not yet been studied, we hypothesize that mTORC1 signaling pathway in platelets may play an important role in arterial thrombosis.
Methods and Results: To determine the role of platelet TSC1 in arterial thrombosis, we generated a mouse strain with platelet-specific TSC1 deficiency (PF4Cre-TSC1flox/+) using conditional TSC1flox/flox mice and platelet-specific PF4-Cre mice. PF4Cre-TSC1flox/+ mice did not show any obvious phenotypic abnormalities. Arterial thrombus formation was investigated using in vivo ferric chloride induced thrombosis model. Ferric Chloride (5% FeCl3) induced thrombotic occlusion. Compared to PF4-Cre mice, PF4Cre-TSC1flox/+ mice exhibited elongated thrombotic occlusion time by 21.7%. Platelet specific TSC1 deficiency promotes arterial thrombosis via activation of mTOR and S6, a downstream target of mTORC1.
Conclusion: These finding indicate that platelet specific TSC1 deficiency promotes arterial thrombosis in vivo. These results suggest that activation of mTORC1 may have therapeutic benefits in arterial thrombosis.
- © 2012 by American Heart Association, Inc.