{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T10:45:19Z","timestamp":1758278719569},"reference-count":9,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Murine atherosclerosis models do not spontaneously develop atherothrombotic complications. We investigated whether disruption of natural anticoagulation allows preexisting atherosclerotic plaques to progress toward an atherothrombotic phenotype.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              On lowering of plasma protein C levels with small interfering RNA (si\n              <jats:italic>Proc<\/jats:italic>\n              ) in 8-week Western-type diet\u2013fed atherosclerotic apolipoprotein E\u2013deficient mice, 1 out of 4 mice displayed a large, organized, and fibrin- and leukocyte-rich thrombus on top of an advanced atherosclerotic plaque located in the aortic root. Although again at low incidence (3 in 25), comparable thrombi at the same location were observed during a second independent experiment in 9-week Western-type diet\u2013fed apolipoprotein E\u2013deficient mice. Mice with thrombi on their atherosclerotic plaques did not show other abnormalities and had equally lowered plasma protein C levels as si\n              <jats:italic>Proc<\/jats:italic>\n              -treated apolipoprotein E\u2013deficient mice without thrombi. Fibrinogen and thrombin\u2013antithrombin concentrations and blood platelet numbers were also comparable, and plaques in si\n              <jats:italic>Proc<\/jats:italic>\n              mice with thrombi had a similar composition and size as plaques in si\n              <jats:italic>Proc<\/jats:italic>\n              mice without thrombi. Seven out of 25 si\n              <jats:italic>Proc<\/jats:italic>\n              mice featured clots in the left atrium of the heart.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Our findings indicate that small interfering RNA\u2013mediated silencing of protein C in apolipoprotein E\u2013deficient mice creates a condition that allows the occurrence of spontaneous atherothrombosis, albeit at a low incidence. Lowering natural anticoagulation in atherosclerosis models may help to discover factors that increase atherothrombotic complications.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.117.309188","type":"journal-article","created":{"date-parts":[[2017,3,17]],"date-time":"2017-03-17T01:10:36Z","timestamp":1489713036000},"page":"782-785","update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Silencing of Anticoagulant Protein C Evokes Low-Incident but Spontaneous Atherothrombosis in Apolipoprotein E\u2013Deficient Mice\u2014Brief Report"],"prefix":"10.1161","volume":"37","author":[{"given":"Amber B.","family":"Ouweneel","sequence":"first","affiliation":[{"name":"From the Division of Biopharmaceutics, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, The Netherlands (A.B.O., R.A.F.V., M.v.E.); Einthoven Laboratory for Experimental Vascular Medicine (M.H., P.H.R., B.J.M.v.V.), and Department of Internal Medicine, Division of Thrombosis and Hemostasis (M.H., P.H.R., B.J.M.v.V.), Leiden University Medical Center, The Netherlands; Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, The Netherlands ..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Heestermans","sequence":"additional","affiliation":[{"name":"From the Division of Biopharmaceutics, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, The Netherlands (A.B.O., R.A.F.V., M.v.E.); Einthoven Laboratory for Experimental Vascular Medicine (M.H., P.H.R., B.J.M.v.V.), and Department of Internal Medicine, Division of Thrombosis and Hemostasis (M.H., P.H.R., B.J.M.v.V.), Leiden University Medical Center, The Netherlands; Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, The Netherlands ..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin A.F.","family":"Verwilligen","sequence":"additional","affiliation":[{"name":"From the Division of Biopharmaceutics, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, The Netherlands (A.B.O., R.A.F.V., M.v.E.); Einthoven Laboratory for Experimental Vascular Medicine (M.H., P.H.R., B.J.M.v.V.), and Department of Internal Medicine, Division of Thrombosis and Hemostasis (M.H., P.H.R., B.J.M.v.V.), Leiden University Medical Center, The Netherlands; Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, The Netherlands ..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion J.J.","family":"Gijbels","sequence":"additional","affiliation":[{"name":"From the Division of Biopharmaceutics, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, The Netherlands (A.B.O., R.A.F.V., M.v.E.); Einthoven Laboratory for Experimental Vascular Medicine (M.H., P.H.R., B.J.M.v.V.), and Department of Internal Medicine, Division of Thrombosis and Hemostasis (M.H., P.H.R., B.J.M.v.V.), Leiden University Medical Center, The Netherlands; Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, The Netherlands ..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieter H.","family":"Reitsma","sequence":"additional","affiliation":[{"name":"From the Division of Biopharmaceutics, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, The Netherlands (A.B.O., R.A.F.V., M.v.E.); Einthoven Laboratory for Experimental Vascular Medicine (M.H., P.H.R., B.J.M.v.V.), and Department of Internal Medicine, Division of Thrombosis and Hemostasis (M.H., P.H.R., B.J.M.v.V.), Leiden University Medical Center, The Netherlands; Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, The Netherlands ..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miranda","family":"Van Eck","sequence":"additional","affiliation":[{"name":"From the Division of Biopharmaceutics, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, The Netherlands (A.B.O., R.A.F.V., M.v.E.); Einthoven Laboratory for Experimental Vascular Medicine (M.H., P.H.R., B.J.M.v.V.), and Department of Internal Medicine, Division of Thrombosis and Hemostasis (M.H., P.H.R., B.J.M.v.V.), Leiden University Medical Center, The Netherlands; Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, The Netherlands ..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart J.M.","family":"van Vlijmen","sequence":"additional","affiliation":[{"name":"From the Division of Biopharmaceutics, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, The Netherlands (A.B.O., R.A.F.V., M.v.E.); Einthoven Laboratory for Experimental Vascular Medicine (M.H., P.H.R., B.J.M.v.V.), and Department of Internal Medicine, Division of Thrombosis and Hemostasis (M.H., P.H.R., B.J.M.v.V.), Leiden University Medical Center, The Netherlands; Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, The Netherlands ..."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2011.91"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.8.2013"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddmod.2007.06.001"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02719.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep10225"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055784"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-11-465674"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-02-558940"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.13.4222"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.117.309188","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:17:17Z","timestamp":1715555837000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.117.309188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5]]},"references-count":9,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,5]]}},"alternative-id":["10.1161\/ATVBAHA.117.309188"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.117.309188","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5]]},"assertion":[{"value":"2016-10-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-03-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-03-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}