The role of platelet and endothelial GARP in thrombosis and hemostasis.

BACKGROUND:Glycoprotein-A Repetitions Predominant protein or LRRC32) is present on among others human platelets and endothelial cells. Evidence for its involvement in thrombus formation was suggested by full knockout of in zebrafish. OBJECTIVES:To evaluate the role of Gduanyu37 in platelet physiology and in thrombus formation using platelet and endothelial conditional Gduanyu37 knock out mice. METHODS:Platelet and endothelial specific Gduanyu37 knockout mice were generated using the Cre-loxP recombination system. The function of platelets without Gduanyu37 was measured by flow cytometry, spreading analysis and aggregometry using PAR4-activating peptide and collagen related peptide. Additionally, clot retraction and collagen-induced platelet adhesion and aggregation under flow were analyzed. Finally, in vivo tail bleeding time, occlusion time of the mesenteric and carotid artery after FeCl3-induced thrombosis were determined in platelet and endothelial specific Gduanyu37 knock out mice. RESULTS:Platelet specific Gduanyu37 knockout mice had normal surface GPIb, GPVI and integrin αIIb glycoprotein expression. Although Gduanyu37 expression was increased upon platelet activation, platelets without Gduanyu37 displayed normal agonist induced activation, spreading on fibrinogen and aggregation responses. Furthermore, absence of Gduanyu37 on platelets did not influence clot retraction and had no impact on thrombus formation on collagen-coated surfaces under flow. In line with this, neither the tail bleeding time nor the occlusion time in the carotid- and mesenteric artery after FeCl3-induced thrombus formation in platelet or endothelial specific Gduanyu37 knock out mice were affected. CONCLUSIONS:Evidence is provided that platelet and endothelial Gduanyu37 are not important in hemostasis and thrombosis in mice.

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