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Blood, 15 July 2006, Vol. 108, No. 2, pp. 510-514.
Prepublished online as a Blood First Edition Paper on February 28, 2006; DOI 10.1182/blood-2005-12-4835.
Previous Article | Next Article 
Submitted December 6, 2005
Accepted February 6, 2006
Reduced thrombus stability in mice lacking the 2A-adrenergic receptor
Miroslava Pozgajova, Ulrich J Sachs, Lutz Hein, and Bernhard Nieswandt*
Rudolf Virchow Center, DFG Center for Experimental Biomedicine, University of Wurzburg, Wurzburg, Germany
Institute of Pharmacology and Toxicology, University of Freiburg, Freiburg, Germany
Rudolf Virchow Center, DFG Center for Experimental Biomedicine, University of Wurzburg, Wurzburg, Germany; Institute of Clinical Biochemistry and Pathobiochemistry, University of Wurzburg, Wurzburg, Germany
* Corresponding author; email: bernhard.nieswandt{at}virchow.uni-wuerzburg.de.
Platelet activation plays a central role in hemostasis and thrombosis. Many platelet agonists function through G-protein coupled receptors. Epinephrine activates the 2A-adrenergic receptor ( 2A) that couples to Gz in platelets. Although 2A was originally cloned from platelets, its role in thrombosis and hemostasis is still unclear. Analyzing 2A-deficient mice, variable tail bleeding times were observed. In vitro, epinephrine potentiated activation/aggregation responses of wild type, but not 2A-deficient platelets as determined by flow cytometry and aggregometry, whereas perfusion studies showed no differences in platelet adhesion and thrombus formation on collagen. To test the in vivo relevance of 2A-deficiency, mice were subjected to three different thrombosis models. As expected, 2A-deficient mice were largely protected from lethal pulmonary thromboembolism induced by the infusion of collagen/epinephrine. In a model of FeCl3-induced injury in mesenteric arterioles, 2A-/- mice displayed a two fold increase in embolus formation, suggesting thrombus instability. In a third model, the aorta was mechanically injured and blood flow was measured with an ultrasonic flow probe. In wild type mice, all vessels occluded irreversibly, whereas in 24% of 2A-deficient mice the initially formed thrombi embolized and blood flow was re-established. These results demonstrate that 2A plays a significant role in thrombus stabilization.

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