{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:12:27Z","timestamp":1791231147912,"version":"4.1.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2013,1,23]]},"abstract":"<jats:sec xml:lang=\"en\"><jats:title>Background<\/jats:title><jats:p xml:lang=\"en\">Platelet activation is central to the pathogenesis of acute coronary syndromes. Surface expression of<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\u2010selectin on activated platelets induces formation of platelet\u2013monocyte aggregates and promotes vascular inflammation and thrombosis.<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\u2010selectin antagonism may represent a novel therapeutic strategy in vascular disease. We aimed to investigate the effects of the novel<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\u2010selectin antagonist<jats:styled-content style=\"fixed-case\">PSI<\/jats:styled-content>\u2010697 on platelet\u2013monocyte aggregate formation in humans.<\/jats:p><\/jats:sec><jats:sec xml:lang=\"en\"><jats:title>Methods and Results<\/jats:title><jats:p xml:lang=\"en\">In a double\u2010blind, randomized, placebo\u2010controlled crossover study, healthy smokers were randomized to receive either oral<jats:styled-content style=\"fixed-case\">PSI<\/jats:styled-content>\u2010697 600\u00a0mg or matched placebo. The sequence of treatment was also randomized, with all subjects receiving both<jats:styled-content style=\"fixed-case\">PSI<\/jats:styled-content>\u2010697 and placebo. Platelet\u2013monocyte aggregates were measured by flow cytometry at 4 and 24\u00a0hours in the presence and absence of thrombin receptor\u2010activating peptide (<jats:styled-content style=\"fixed-case\">TRAP<\/jats:styled-content>; 0.1 to 1.0\u00a0\u03bcm\/L). The<jats:italic>ex vivo<\/jats:italic>addition of<jats:styled-content style=\"fixed-case\">TRAP<\/jats:styled-content>caused a concentration\u2010dependent increase in platelet\u2013monocyte aggregates from 8.2% to 94.8% (<jats:italic>P<\/jats:italic>&lt;0.001). At 4 and 24\u00a0hours, plasma concentrations of<jats:styled-content style=\"fixed-case\">PSI<\/jats:styled-content>\u2010697 increased to 1906 and 83\u00a0ng\/mL, respectively (<jats:italic>P<\/jats:italic>&lt;0.001).<jats:styled-content style=\"fixed-case\">PSI<\/jats:styled-content>\u2010697 had no demonstrable effect on either stimulated or unstimulated platelet\u2013monocyte aggregates at 4 or 24\u00a0hours (<jats:italic>P<\/jats:italic>&gt;0.05).<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\u2010selectin\u2010blocking antibody (<jats:styled-content style=\"fixed-case\">CLB<\/jats:styled-content>\u2010Thromb6), but not<jats:styled-content style=\"fixed-case\">PSI<\/jats:styled-content>\u2010697, inhibited both stimulated and unstimulated platelet\u2013monocyte aggregate formation in vitro (<jats:italic>P<\/jats:italic>&lt;0.001).<\/jats:p><\/jats:sec><jats:sec xml:lang=\"en\"><jats:title>Conclusions<\/jats:title><jats:p xml:lang=\"en\">The novel small\u2010molecule<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\u2010selectin antagonist<jats:styled-content style=\"fixed-case\">PSI<\/jats:styled-content>\u2010697 did not inhibit basal or stimulated platelet\u2013monocyte aggregate formation in humans at the dose tested. Its clinical efficacy remains to be established.<\/jats:p><\/jats:sec><jats:sec xml:lang=\"en\"><jats:title>Clinical Trial Registration<\/jats:title><jats:p xml:lang=\"en\"><jats:styled-content style=\"fixed-case\">URL<\/jats:styled-content>:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/EudraCT.ema.europa.eu\">http:\/\/EudraCT.ema.europa.eu<\/jats:ext-link>Unique identifier: 2007\u2010005695\u201014.<\/jats:p><\/jats:sec>","DOI":"10.1161\/jaha.112.006007","type":"journal-article","created":{"date-parts":[[2013,5,24]],"date-time":"2013-05-24T16:49:11Z","timestamp":1369414151000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["Effect of PSI\u2010697, a Novel P\u2010Selectin Inhibitor, on Platelet\u2013Monocyte Aggregate Formation in Humans"],"prefix":"10.1161","volume":"2","author":[{"given":"Alan G.","family":"Japp","sequence":"first","affiliation":[{"name":"Edinburgh Heart Centre, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj","family":"Chelliah","sequence":"additional","affiliation":[{"name":"British Heart Foundation\/University Centre for Cardiovascular Science, University of Edinburgh, 49 Little France Crescent, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Tattersall","sequence":"additional","affiliation":[{"name":"British Heart Foundation\/University Centre for Cardiovascular Science, University of Edinburgh, 49 Little France Crescent, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ninian N.","family":"Lang","sequence":"additional","affiliation":[{"name":"British Heart Foundation\/University Centre for Cardiovascular Science, University of Edinburgh, 49 Little France Crescent, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Meng","sequence":"additional","affiliation":[{"name":"Wyeth Research, Collegeville, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Weisel","sequence":"additional","affiliation":[{"name":"Wyeth Research, Collegeville, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie","family":"Katz","sequence":"additional","affiliation":[{"name":"Wyeth Research, Collegeville, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Burt","sequence":"additional","affiliation":[{"name":"Wyeth Research, Collegeville, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A. 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