{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T23:14:16Z","timestamp":1789859656588,"version":"4.0.1"},"reference-count":70,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,5,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Platelets are the cellular mediators of hemostasis and thrombosis, and their function is regulated by a number of molecular mediators, such as small\n              <jats:styled-content style=\"fixed-case\">GTP<\/jats:styled-content>\n              ases. These small\n              <jats:styled-content style=\"fixed-case\">GTP<\/jats:styled-content>\n              ases are themselves regulated by guanine nucleotide exchange factors such as Arhgefs, several of which are found in platelets, including the highly expressed Arhgef1. However, the role of Arhgef1 in platelets has not yet been investigated.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We employed mice with genetic deletion of Arhgef1 (ie, Arhgef1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              ) and investigated their platelet phenotype by employing a host of in\u00a0vivo and in\u00a0vitro platelet assays. Our results indicate that Arhgef1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice had prolonged carotid artery occlusion and tail bleeding times. Moreover, platelets from these mice exhibited defective aggregation, dense and \u03b1 granule secretion, \u03b1\n              <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>\n              b\u03b23 integrin activation, clot retraction and spreading, in comparison to their wild\u2010type littermates. Finally, we also found that the mechanism by which Arhgef1 regulates platelets is mediated in part by a defect in the activation of the RhoA\u2013Rho\u2010associated kinase axis, but not Rap1b.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our data demonstrate, for the first time, that Arhgef1 plays a critical role in platelet function, in\u00a0vitro and in\u00a0vivo.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.118.011712","type":"journal-article","created":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T09:07:13Z","timestamp":1555492033000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Arhgef1 Plays a Vital Role in Platelet Function and Thrombogenesis"],"prefix":"10.1161","volume":"8","author":[{"given":"Hanan","family":"Qasim","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy The University of Texas El Paso El Paso TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zubair A.","family":"Karim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy The University of Texas El Paso El Paso TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keziah R.","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy The University of Texas El Paso El Paso TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dante","family":"Lozano","sequence":"additional","affiliation":[{"name":"El Paso Community College El Paso TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadi 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