{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:34:54Z","timestamp":1790418894988,"version":"4.1.0"},"reference-count":66,"publisher":"Georg Thieme Verlag KG","issue":"12","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health NIH","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2014]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The pathogenesis of atherosclerosis involves the interplay of haematopoietic, stromal and endothelial cells. Platelet interactions with endothelium and leukocytes are pivotal for atherosclerosis promotion. Glycoprotein (GP) Ib\u03b1 is the ligand-binding subunit of the platelet GPIb-IX-V receptor complex; its deficiency causes the Bernard-Soulier syndrome (BSS), characterised by absent platelet GPIb-IX-V, macrothrombocytopenia and bleeding. We designed this study to determine the role of platelet GPIb\u03b1 in the pathogenesis of atherosclerosis using two unique knockout models. Ldlr-\/- mice were reconstituted with wild-type (wt), GPIb\u03b1-\/- (lacks GPIb\u03b1) or chimeric IL-4R\/GPIb\u03b1-Tg (lacks GPIb\u03b1 extracellular domain) bone marrow and assayed for atherosclerosis development after feeding with pro-atherogenic \u201cwestern diet\u201d. Here, we report that Ldlr-\/- mice reconstituted with GPIb\u03b1-\/- bone marrow developed less atherosclerosis compared to wt controls; accompanied by augmented accumulation of pro-inflammatory CD11b+ and CD11c+ myeloid cells, reduced oxLDL uptake and decreased TNF and IL 12p35 gene expression in the aortas. Flow cytometry and live cell imaging in whole blood-perfused microfluidic chambers revealed reduced platelet-monocyte aggregates in GPIb\u03b1-\/- mice, which resulted in decreased monocyte activation. Interestingly, Ldlr -\/- mice reconstituted with IL-4R\/GPIb\u03b1-Tg bone marrow, producing less abnormal platelets, showed atherosclerotic lesions similar to wt mice. Platelet interaction with blood monocytes and accumulation of myeloid cells in the aortas were also essentially unaltered. Moreover, only complete GPIb\u03b1 ablation altered platelet microparticles and CCL5 chemokine production. Thus, atherosclerosis reduction in mice lacking GPIb\u03b1 may not result from the defective GPIb\u03b1-ligand binding, but more likely is a consequence of functional defects of GPIb\u03b1-\/- platelets and reduced blood platelet counts.<\/jats:p>","DOI":"10.1160\/th14-02-0130","type":"journal-article","created":{"date-parts":[[2014,8,8]],"date-time":"2014-08-08T06:19:59Z","timestamp":1407478799000},"page":"1252-1263","source":"Crossref","is-referenced-by-count":27,"title":["Genetic deletion of platelet glycoprotein Ib alpha but not its extracellular domain protects from 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