Mar 1, 2017

Receptor-interacting protein kinase 3 promotes platelet activation and thrombosis

Proceedings of the National Academy of Sciences of the United States of America
Yiwen ZhangKesheng Dai

Abstract

Previous studies have shown that receptor-interacting protein kinase 3 (RIP3) is involved in many important biological processes, including necroptosis, apoptosis, and inflammation. Here we show that RIP3 plays a critical role in regulating platelet functions and in vivo thrombosis and hemostasis. Tail bleeding times were significantly longer in RIP3-knockout (RIP3-/-) mice compared with their wild-type (WT) littermates. In an in vivo model of arteriole thrombosis, mice lacking RIP3 exhibited prolonged occlusion times. WT mice repopulated with RIP3-/- bone marrow-derived cells had longer occlusion times than RIP3-/- mice repopulated with WT bone marrow-derived cells, suggesting a role for RIP3-deficient platelets in arterial thrombosis. Consistent with these findings, we observed that RIP3 was expressed in both human and mice platelets. Deletion of RIP3 in mouse platelets caused a marked defect in aggregation and attenuated dense granule secretion in response to low doses of thrombin or a thromboxane A2 analog, U46619. Phosphorylation of Akt induced by U46619 or thrombin was diminished in RIP3-/- platelets. Moreover, RIP3 interacted with Gα13 Platelet spreading on fibrinogen and clot retraction were impaired in the absence of R...Continue Reading

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References

  • References1
  • Citations3

Mentioned in this Paper

Pathologic Cytolysis
Peptide Nucleic Acids
Entire Arteriole
Study
Thromboxane A2
SELP gene
In Vivo
GP1BA
ITGA2B gene
Flow Cytometry

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