{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:57:56Z","timestamp":1791899876667,"version":"4.3.4"},"reference-count":140,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:00:00Z","timestamp":1666137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China Scholarship Council","award":["201909370052"],"award-info":[{"award-number":["201909370052"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Integrin \u03b1IIb\u03b23 activation is essential for platelet aggregation and, accordingly, for hemostasis and arterial thrombosis. The \u03b1IIb\u03b23 integrin is highly expressed on platelets and requires an activation step for binding to fibrinogen, fibrin or von Willebrand factor (VWF). A current model assumes that the process of integrin activation relies on actomyosin force-dependent molecular changes from a bent-closed and extended-closed to an extended-open conformation. In this paper we review the pathways that point to a functional reversibility of platelet \u03b1IIb\u03b23 activation and transient aggregation. Furthermore, we refer to mouse models indicating that genetic defects that lead to reversible platelet aggregation can also cause instable thrombus formation. We discuss the platelet agonists and signaling pathways that lead to a transient binding of ligands to integrin \u03b1IIb\u03b23. Our analysis points to the (autocrine) ADP P2Y1 and P2Y12 receptor signaling via phosphoinositide 3-kinases and Akt as principal pathways linked to reversible integrin activation. Downstream signaling events by protein kinase C, CalDAG-GEFI and Rap1b have not been linked to transient integrin activation. Insight into the functional reversibility of integrin activation pathways will help to better understand the effects of antiplatelet agents.<\/jats:p>","DOI":"10.3390\/ijms232012512","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T20:32:23Z","timestamp":1666211543000},"page":"12512","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Reversible Platelet Integrin \u03b1IIb\u03b23 Activation and Thrombus Instability"],"prefix":"10.3390","volume":"23","author":[{"given":"Jinmi","family":"Zou","sequence":"first","affiliation":[{"name":"Synapse Research Institute Maastricht, Koningin Emmaplein 7, 6217 KD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"Swieringa","sequence":"additional","affiliation":[{"name":"Synapse Research Institute Maastricht, Koningin Emmaplein 7, 6217 KD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bas","family":"de Laat","sequence":"additional","affiliation":[{"name":"Synapse Research Institute Maastricht, Koningin Emmaplein 7, 6217 KD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip G.","family":"de Groot","sequence":"additional","affiliation":[{"name":"Synapse Research Institute Maastricht, Koningin Emmaplein 7, 6217 KD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Roest","sequence":"additional","affiliation":[{"name":"Synapse Research Institute Maastricht, Koningin Emmaplein 7, 6217 KD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2848-5121","authenticated-orcid":false,"given":"Johan W. M.","family":"Heemskerk","sequence":"additional","affiliation":[{"name":"Synapse Research Institute Maastricht, Koningin Emmaplein 7, 6217 KD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0092-8674(02)00971-6","article-title":"Integrins: Bidirectional, allosteric signaling machines","volume":"110","author":"Hynes","year":"2002","journal-title":"Cell"},{"key":"ref_2","unstructured":"Michelson, A.D. (2007). Integrin \u03b1IIb\u03b23. 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