{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:05:32Z","timestamp":1790258732307,"version":"4.1.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>PI3K\u03b1 (phosphoinositide 3-kinase alpha) is a therapeutic target in oncology, but its role in platelets and thrombosis remains ill characterized. In this study, we have analyzed the role of PI3K\u03b1 in vitro, ex vivo, and in vivo in 2 models of arterial thrombosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Using mice selectively deficient in p110\u03b1 in the megakaryocyte lineage and isoform-selective inhibitors, we confirm that PI3K\u03b1 is not mandatory but participates to thrombus growth over a collagen matrix at arterial shear rate. Our data uncover a role for PI3K\u03b1 in low-level activation of the GP (glycoprotein) VI-collagen receptor by contributing to ADP secretion and in turn full activation of PI3K\u03b2 and Akt\/PKB (protein kinase B). This effect was no longer observed at high level of GP VI agonist concentration. Our study also reveals that over a vWF (von Willebrand factor) matrix, PI3K\u03b1 regulates platelet stationary adhesion contacts under arterial flow through its involvement in the outside-in signaling of vWF-engaged \u03b1\n              <jats:sub>IIb<\/jats:sub>\n              \u03b2\n              <jats:sub>3<\/jats:sub>\n              integrin. In vivo, absence or inhibition of PI3K\u03b1 resulted in a modest but significant decrease in thrombus size after superficial injuries of mouse mesenteric arteries and an increased time to arterial occlusion after carotid lesion, without modification in the tail bleeding time. Considering the more discrete and nonredundant role of PI3K\u03b1 compared with PI3K\u03b2, selective PI3K\u03b1 inhibitors are unlikely to increase the bleeding risk at least in the absence of combination with antiplatelet drugs or thrombopenia.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>This study provides mechanistic insight into the role of PI3K\u03b1 in platelet activation and arterial thrombosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.118.311410","type":"journal-article","created":{"date-parts":[[2018,9,16]],"date-time":"2018-09-16T08:39:42Z","timestamp":1537087182000},"page":"2041-2053","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["Impact of PI3K\u03b1 (Phosphoinositide 3-Kinase Alpha) Inhibition on Hemostasis and Thrombosis"],"prefix":"10.1161","volume":"38","author":[{"given":"Pierre-Alexandre","family":"Laurent","sequence":"first","affiliation":[{"name":"From the INSERM, UMR-S1048, Universit\u00e9 Toulouse III, France (P.-A.L., R.S., A.R., C.C., T.A., S.S., B.P., M.-P.G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9atrice","family":"Hechler","sequence":"additional","affiliation":[{"name":"INSERM, EFS Grand Est, BPPS UMR-S 949, FMTS, Universit\u00e9 de Strasbourg, France (B.H., P.H.M.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Solinhac","sequence":"additional","affiliation":[{"name":"From the INSERM, UMR-S1048, Universit\u00e9 Toulouse III, France (P.-A.L., R.S., A.R., C.C., T.A., S.S., B.P., M.-P.G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf","family":"Ragab","sequence":"additional","affiliation":[{"name":"From the INSERM, UMR-S1048, Universit\u00e9 Toulouse III, France (P.-A.L., R.S., A.R., 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