| First Author | Ahmad F | Year | 2011 |
| Journal | J Thromb Haemost | Volume | 9 |
| Issue | 10 | Pages | 2077-86 |
| PubMed ID | 21848641 | Mgi Jnum | J:341173 |
| Mgi Id | MGI:7531892 | Doi | 10.1111/j.1538-7836.2011.04474.x |
| Citation | Ahmad F, et al. (2011) Relative contributions of stromal interaction molecule 1 and CalDAG-GEFI to calcium-dependent platelet activation and thrombosis. J Thromb Haemost 9(10):2077-86 |
| abstractText | BACKGROUND: Stromal interaction molecule 1 (STIM1) was recently identified as a critical component of store-operated calcium entry (SOCE) in platelets. We previously reported the Ca(2+) -sensing guanine nucleotide exchange factor CalDAG-GEFI as a critical molecule in Ca(2+) signaling in platelets. OBJECTIVE: To evaluate the contribution of STIM1/SOCE to Ca(2+) -dependent platelet activation and thrombosis, we here compared the activation responses of platelets lacking STIM1 and platelets lacking CalDAG-GEFI. METHODS: The murine Stim1 gene was conditionally deleted in the megakaryocyte/platelet lineage. CalDAG-GEFI(-/-) and Stim1(fl/fl) PF4-Cre mice, along with littermate control mice, were used for in vitro and in vivo experiments under flow as well as static conditions. RESULTS: Integrin alpha(IIb) beta(3) -mediated aggregation was markedly impaired in CalDAG-GEFI-deficient but not STIM1-deficient platelets, under both static and flow conditions. In contrast, deficiency in either STIM1 or CalDAG-GEFI significantly impaired the ability of platelets to express phosphatidylserine on the cell surface. When subjected to a laser injury thrombosis model, mice lacking STIM1 in platelets were characterized by the formation of unstable platelet-rich thrombi and delayed and reduced fibrin generation in injured arterioles. In CalDAG-GEFI(-/-) mice, fibrin generation was also delayed and reduced, but platelet accumulation was almost abolished. CONCLUSIONS: Our studies suggest that: (i) STIM1/SOCE is critical for the procoagulant activity but not the proadhesive function of platelets; and (ii) at the site of vascular injury, STIM1 and CalDAG-GEFI are critical for the first wave of thrombin generation mediated by procoagulant platelets. |
