{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:33:24Z","timestamp":1760783604252,"version":"3.40.4"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,5,27]],"date-time":"2013-05-27T00:00:00Z","timestamp":1369612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The glycoprotein<jats:styled-content style=\"fixed-case\">IIb<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">IIIa<\/jats:styled-content>receptor is the final common pathway of platelet aggregation, regardless of the agonist, and thus represents an ideal therapeutic target for blocking coronary thrombosis. In this study, the anti\u2010platelet and antithrombotic actions of<jats:styled-content style=\"fixed-case\">Z4A5<\/jats:styled-content>, a new glycoprotein<jats:styled-content style=\"fixed-case\">IIb<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">IIIa<\/jats:styled-content>receptor inhibitor, were evaluated in a canine model of acute unstable angina.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">Z4A5<\/jats:styled-content>was given i.v. as a bolus followed by 60\u2009min of continuous infusion at doses of 30\u2009\u03bcg\u00b7kg<jats:sup>\u22121<\/jats:sup>+ 1\u2009\u03bcg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup>, 30\u2009\u03bcg\u00b7kg<jats:sup>\u22121<\/jats:sup>+ 5\u2009\u03bcg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup>or 300\u2009\u03bcg\u00b7kg<jats:sup>\u22121<\/jats:sup>+ 5\u2009\u03bcg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup>. Its antithrombotic effect was evaluated in a model of coronary thrombosis, the injured, stenosed left circumflex coronary artery, in which platelet\u2010dependent cyclic flow reductions (CFRs) were induced by vascular compression and constriction to simulate clinical acute unstable angina. Platelet aggregation and coagulation parameters were determined in platelet\u2010rich plasma and platelet poor plasma respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The<jats:styled-content style=\"fixed-case\">Z4A5<\/jats:styled-content>infusion induced a dose\u2010dependent reduction in<jats:styled-content style=\"fixed-case\">CFR<\/jats:styled-content>frequency, which returned to baseline levels after the termination of the infusion at low doses. At medium dose that inhibited most part of platelet aggregation, it increased tongue bleeding time marginally with no dramatic changes in haemodynamic and coagulation parameters. Furthermore, the inhibition of<jats:styled-content style=\"fixed-case\">ADP<\/jats:styled-content>\u2010induced platelet aggregation and prolonged bleeding time observed during<jats:styled-content style=\"fixed-case\">Z4A5<\/jats:styled-content>infusion reverted to baseline levels after the termination of the infusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">Z4A5<\/jats:styled-content>is an effective antithrombotic agent for coronary artery thrombosis with a rapid\u2010on and rapid\u2010off pharmacological profile, and could be used as an alternative treatment of coronary artery ischaemic syndromes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12026","type":"journal-article","created":{"date-parts":[[2012,10,19]],"date-time":"2012-10-19T12:21:49Z","timestamp":1350649309000},"page":"848-859","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Antithrombotic effect of<scp>Z4A5<\/scp>on coronary thrombosis in a canine model of acute unstable angina"],"prefix":"10.1111","volume":"169","author":[{"given":"Bo\u2010Bin","family":"Jing","sequence":"first","affiliation":[{"name":"School of Medicine Xi'an Jiaotong University Xi'an Shaanxi China"},{"name":"National Vaccine and Serum Institute Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying\u2010Xue","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine Xi'an Jiaotong University Xi'an Shaanxi China"},{"name":"Therapeutic Vaccines Engineering Center Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine Xi'an Jiaotong University Xi'an Shaanxi China"},{"name":"Therapeutic Vaccines Engineering Center Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu\u2010Ting","family":"Ren","sequence":"additional","affiliation":[{"name":"School of Medicine Xi'an Jiaotong University Xi'an Shaanxi China"},{"name":"Therapeutic Vaccines Engineering Center Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Wang","sequence":"additional","affiliation":[{"name":"Second Hospital Xi'an Jiaotong University Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Ping","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine Xi'an Jiaotong University Xi'an Shaanxi China"},{"name":"Therapeutic Vaccines Engineering Center Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin\u2010Liang","family":"Shen","sequence":"additional","affiliation":[{"name":"China National Biotec Group Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Li","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine Xi'an Jiaotong University Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010Jin","family":"Zang","sequence":"additional","affiliation":[{"name":"School of Medicine Xi'an Jiaotong University Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine Xi'an Jiaotong University Xi'an Shaanxi China"},{"name":"Therapeutic Vaccines Engineering Center Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,5,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.620815"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(94)90586-X"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjp.2008.151"},{"key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1055\/s-0038-1653449","article-title":"In vitro effect of ethanol on ADP and collagen\u2010induced platelet aggregation","volume":"46","author":"Bengmark S","year":"1981","journal-title":"Thromb Haemost"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.52.1.161"},{"key":"e_1_2_8_7_1","first-page":"204","article-title":"Inhibition of epinephrine\u2010exacerbated coronary thrombus formation by prostacyclin in the dog","volume":"103","author":"Bertha BG","year":"1984","journal-title":"J Lab Clin Med"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.21.2219"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)02336-7"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.2.201"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(01)00353-X"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-010-6259-3"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(91)90702-B"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199905273402103"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/heart.88.1.11"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1538-7836.2003.00267.x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH09-03-0192"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2011.08.003"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-200206000-00016"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.25.2829"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(90)90106-M"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2012.02.047"},{"key":"e_1_2_8_23_1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/S0022-3565(25)24307-5","article-title":"Nonpeptide glycoprotein IIb\/IIIa inhibitors. 5. Antithrombotic effects of MK\u20100383","volume":"272","author":"Lynch JJ","year":"1995","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.95.4.1015"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00873.x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90451-4"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.23.8057"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011216414539"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03432.x"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8183.2006.00182.x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2011.11.053"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.10.3623"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ultras.2010.09.001"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.12026","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.12026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T22:04:02Z","timestamp":1744668242000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.12026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,27]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,6]]}},"alternative-id":["10.1111\/bph.12026"],"URL":"https:\/\/doi.org\/10.1111\/bph.12026","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"type":"print","value":"0007-1188"},{"type":"electronic","value":"1476-5381"}],"subject":[],"published":{"date-parts":[[2013,5,27]]},"assertion":[{"value":"2011-11-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-09-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-05-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}