{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:05:04Z","timestamp":1789758304136,"version":"4.0.1"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>\n              Low-dose aspirin is widely used for the secondary prevention of cardiovascular disease. The beneficial effects of low-dose aspirin are attributable to its inhibition of platelet Cox (cyclooxygenase)-1\u2013derived thromboxane A\n              <jats:sub>2<\/jats:sub>\n              . Until recently, the use of the Pf4 (platelet factor 4) Cre has been the only genetic approach to generating megakaryocyte\/platelet ablation of Cox-1 in mice. However, Pf4-\u0394Cre displays ectopic expression outside the megakaryocyte\/platelet lineage, especially during inflammation. The use of the Gp1ba (glycoprotein 1b\u03b1) Cre promises a more specific, targeted approach.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              To evaluate the role of Cox-1 in platelets, we crossed Pf4-\u0394Cre or Gp1ba-\u0394Cre mice with Cox-1\n              <jats:sup>flox\/flox<\/jats:sup>\n              mice to generate platelet Cox-1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice on normolipidemic and hyperlipidemic (Ldlr\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              ; low-density lipoprotein receptor) backgrounds.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Ex vivo platelet aggregation induced by arachidonic acid or adenosine diphosphate in platelet-rich plasma was inhibited to a similar extent in Pf4-\u0394Cre Cox-1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              \/Ldlr\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              and Gp1ba-\u0394Cre Cox-1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              \/Ldlr\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice. In a mouse model of tail injury, Pf4-\u0394Cre\u2013mediated and Gp1ba-\u0394Cre\u2013mediated deletions of Cox-1 were similarly efficient in suppressing platelet prostanoid biosynthesis. Experimental thrombogenesis and attendant blood loss were similar in both models. However, the impact on atherogenesis was divergent, being accelerated in the Pf4-\u0394Cre mice while restrained in the Gp1ba-\u0394Cres. In the former, accelerated atherogenesis was associated with greater suppression of PGI\n              <jats:sub>2<\/jats:sub>\n              biosynthesis, a reduction in the lipopolysaccharide-evoked capacity to produce PGE\n              <jats:sub>2<\/jats:sub>\n              (prostaglandin E) and PGD\n              <jats:sub>2<\/jats:sub>\n              (prostanglandin D), activation of the inflammasome, elevated plasma levels of IL-1\u03b2 (interleukin), reduced plasma levels of HDL-C (high-density lipoprotein receptor-cholesterol), and a reduction in the capacity for reverse cholesterol transport. By contrast, in the latter, plasma HDL-C and \u03b1-tocopherol were elevated, and MIP-1\u03b1 (macrophage inflammatory protein-1\u03b1) and MCP-1 (monocyte chemoattractant protein 1) were reduced.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Both approaches to Cox-1 deletion similarly restrain thrombogenesis, but a differential impact on Cox-1\u2013dependent prostanoid formation by the vasculature may contribute to an inflammatory phenotype and accelerated atherogenesis in Pf4-\u0394Cre mice.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.123.320295","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T09:01:14Z","timestamp":1714035674000},"page":"1393-1406","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Differential Impact In Vivo of Pf4-\u0394Cre\u2013Mediated and Gp1ba-\u0394Cre\u2013Mediated Depletion of Cyclooxygenase-1 in Platelets in Mice"],"prefix":"10.1161","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8364-0342","authenticated-orcid":true,"given":"Soon Yew","family":"Tang","sequence":"first","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (S.Y.T., R.L., H.M., B.J.A., E.J.H., A.S., U.S.D., R.J., R.M., G.R.G., E.R., T.G., A.M.W., G.A.F.), University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9668-3368","authenticated-orcid":true,"given":"Ronan","family":"Lordan","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (S.Y.T., R.L., H.M., B.J.A., E.J.H., A.S., U.S.D., R.J., R.M., G.R.G., E.R., T.G., A.M.W., G.A.F.), University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2224-5431","authenticated-orcid":true,"given":"Hu","family":"Meng","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (S.Y.T., R.L., H.M., B.J.A., E.J.H., A.S., U.S.D., R.J., R.M., G.R.G., E.R., T.G., A.M.W., G.A.F.), University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0496-1119","authenticated-orcid":true,"given":"Benjamin J.","family":"Auerbach","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (S.Y.T., R.L., H.M., B.J.A., E.J.H., A.S., U.S.D., R.J., R.M., G.R.G., E.R., T.G., A.M.W., G.A.F.), University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Hennessy","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (S.Y.T., R.L., H.M., B.J.A., E.J.H., A.S., U.S.D., R.J., R.M., G.R.G., E.R., T.G., A.M.W., G.A.F.), University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2210-1876","authenticated-orcid":true,"given":"Arjun","family":"Sengupta","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (S.Y.T., R.L., H.M., B.J.A., E.J.H., A.S., U.S.D., R.J., R.M., G.R.G., E.R., T.G., A.M.W., G.A.F.), University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3749-4975","authenticated-orcid":true,"given":"Ujjalkumar S.","family":"Das","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (S.Y.T., R.L., H.M., B.J.A., E.J.H., A.S., U.S.D., R.J., R.M., G.R.G., E.R., T.G., A.M.W., G.A.F.), University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Joshi","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (S.Y.T., R.L., H.M., B.J.A., E.J.H., A.S., U.S.D., R.J., R.M., G.R.G., E.R., T.G., A.M.W., G.A.F.), University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1247-4882","authenticated-orcid":true,"given":"Oscar A.","family":"Marcos-Contreras","sequence":"additional","affiliation":[{"name":"Department of Systems Pharmacology and Translational Therapeutics (O.A.M.-C., E.R., V.R.M., A.M.W.), University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"McConnell","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (S.Y.T., R.L., H.M., B.J.A., E.J.H., A.S., U.S.D., R.J., R.M., G.R.G., E.R., T.G., A.M.W., G.A.F.), University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0139-7658","authenticated-orcid":true,"given":"Gregory R.","family":"Grant","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (S.Y.T., R.L., H.M., B.J.A., E.J.H., A.S., U.S.D., R.J., R.M., G.R.G., E.R., T.G., A.M.W., G.A.F.), University of Pennsylvania, Philadelphia."},{"name":"Department of Genetics (G.R.G., G.A.F.), University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Ricciotti","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (S.Y.T., R.L., H.M., B.J.A., E.J.H., A.S., U.S.D., R.J., R.M., G.R.G., E.R., T.G., A.M.W., G.A.F.), University of Pennsylvania, Philadelphia."},{"name":"Department of Systems Pharmacology and Translational Therapeutics (O.A.M.-C., E.R., V.R.M., A.M.W.), University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6648-1204","authenticated-orcid":true,"given":"Vladimir R.","family":"Muzykantov","sequence":"additional","affiliation":[{"name":"Department of Systems Pharmacology and Translational Therapeutics (O.A.M.-C., E.R., V.R.M., A.M.W.), University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8569-8396","authenticated-orcid":true,"given":"Tilo","family":"Grosser","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (S.Y.T., R.L., H.M., B.J.A., E.J.H., A.S., U.S.D., R.J., R.M., G.R.G., E.R., T.G., A.M.W., G.A.F.), University of Pennsylvania, Philadelphia."},{"name":"Department of Medicine, Perelman School of Medicine (T.G., G.A.F.), University of Pennsylvania, Philadelphia."},{"name":"Now with Department of Translational Pharmacology, Bielefeld University, Germany (T.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7145-4494","authenticated-orcid":true,"given":"Aalim M.","family":"Weiljie","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (S.Y.T., R.L., H.M., B.J.A., E.J.H., A.S., U.S.D., R.J., R.M., G.R.G., E.R., T.G., A.M.W., G.A.F.), University of Pennsylvania, Philadelphia."},{"name":"Department of Systems Pharmacology and Translational Therapeutics (O.A.M.-C., E.R., V.R.M., A.M.W.), University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5885-6819","authenticated-orcid":true,"given":"Garret A.","family":"FitzGerald","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics, Perelman School of Medicine (S.Y.T., R.L., H.M., B.J.A., E.J.H., A.S., U.S.D., R.J., R.M., G.R.G., E.R., T.G., A.M.W., G.A.F.), University of Pennsylvania, Philadelphia."},{"name":"Department of Genetics (G.R.G., G.A.F.), University of Pennsylvania, Philadelphia."},{"name":"Department of Medicine, Perelman School of Medicine (T.G., G.A.F.), University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-051019-102940"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-019-0225-y"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1804988"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.172762"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.02.024"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-09-877787"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12784"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.119.259382"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000312R"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-11-887513"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1080\/09537104.2023.2192289"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3109\/09537104.2011.592958"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(07)33003-6"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.67.6.1174"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1440"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.022308"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003787"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2018.11.005"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-018-0229-2"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41695-z"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-016-1132-4"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac051632c"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25327"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32057"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.048378"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2006348117"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3866"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306361"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.312802"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.061607398"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27540"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198404263101701"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.314927"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1068711"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(87)90103-4"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1103333"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.207449"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000027816.54430.96"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119892"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2017.45"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.584310"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.240462697"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1086\/314559"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.3791\/1488"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.123.320295","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T19:11:11Z","timestamp":1748545871000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.123.320295"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6]]},"references-count":44,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1161\/ATVBAHA.123.320295"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.123.320295","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6]]},"assertion":[{"value":"2023-10-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}