{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T01:16:47Z","timestamp":1789953407674,"version":"4.0.1"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Atherothrombosis is the main cause of myocardial infarction and ischemic stroke. Although the extrinsic (tissue factor\u2013factor VIIa [FVIIa]) pathway is considered as a major trigger of coagulation in atherothrombosis, the role of the intrinsic coagulation pathway via coagulation FXII herein is unknown. Here, we studied the roles of the extrinsic and intrinsic coagulation pathways in thrombus formation on atherosclerotic plaques both in vivo and ex vivo.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Plaque rupture after ultrasound treatment evoked immediate formation of subocclusive thrombi in the carotid arteries of\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\n                <jats:italic>\u2212\/\u2212<\/jats:italic>\n              <\/jats:sup>\n              mice, which became unstable in the presence of structurally different FXIIa inhibitors. In contrast, inhibition of FVIIa reduced thrombus size at a more initial stage without affecting embolization. Genetic deficiency in FXII (human and mouse) or FXI (mouse) reduced ex vivo whole-blood thrombus and fibrin formation on immobilized plaque homogenates. Localization studies by confocal microscopy indicated that FXIIa bound to thrombi and fibrin particularly in luminal-exposed thrombus areas.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>The FVIIa- and FXIIa-triggered coagulation pathways have distinct but complementary roles in atherothrombus formation. The tissue factor\u2013FVIIa pathway contributes to initial thrombus buildup, whereas FXIIa bound to thrombi ensures thrombus stability.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.114.303315","type":"journal-article","created":{"date-parts":[[2014,5,23]],"date-time":"2014-05-23T08:06:01Z","timestamp":1400832361000},"page":"1674-1680","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":108,"title":["Factor XII Regulates the Pathological Process of Thrombus Formation on Ruptured Plaques"],"prefix":"10.1161","volume":"34","author":[{"given":"Marijke J.E.","family":"Kuijpers","sequence":"first","affiliation":[{"name":"From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., P.E.J.v.d.M., M.A.H.F., N.J.A.M., J.G.-R., J.W.M.H., J.M.E.M.C.); CSL Behring GmbH, Marburg, Germany (F.M.); Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (J.C.M.M.); Department of Plasma Proteins, Sanquin, Amsterdam, The Netherlands (J.C.M.M.); Clinical Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola E.J.","family":"van der Meijden","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., P.E.J.v.d.M., M.A.H.F., N.J.A.M., J.G.-R., J.W.M.H., J.M.E.M.C.); CSL Behring GmbH, Marburg, Germany (F.M.); Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (J.C.M.M.); Department of Plasma Proteins, Sanquin, Amsterdam, The Netherlands (J.C.M.M.); Clinical Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion A.H.","family":"Feijge","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., P.E.J.v.d.M., M.A.H.F., N.J.A.M., J.G.-R., J.W.M.H., J.M.E.M.C.); CSL Behring GmbH, Marburg, Germany (F.M.); Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (J.C.M.M.); Department of Plasma Proteins, Sanquin, Amsterdam, The Netherlands (J.C.M.M.); Clinical Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine J.A.","family":"Mattheij","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., P.E.J.v.d.M., M.A.H.F., N.J.A.M., J.G.-R., J.W.M.H., J.M.E.M.C.); CSL Behring GmbH, Marburg, Germany (F.M.); Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (J.C.M.M.); Department of Plasma Proteins, Sanquin, Amsterdam, The Netherlands (J.C.M.M.); Clinical Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"May","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., P.E.J.v.d.M., M.A.H.F., N.J.A.M., J.G.-R., J.W.M.H., J.M.E.M.C.); CSL Behring GmbH, Marburg, Germany (F.M.); Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (J.C.M.M.); Department of Plasma Proteins, Sanquin, Amsterdam, The Netherlands (J.C.M.M.); Clinical Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Govers-Riemslag","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., P.E.J.v.d.M., M.A.H.F., N.J.A.M., J.G.-R., J.W.M.H., J.M.E.M.C.); CSL Behring GmbH, Marburg, Germany (F.M.); Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (J.C.M.M.); Department of Plasma Proteins, Sanquin, Amsterdam, The Netherlands (J.C.M.M.); Clinical Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost C.M.","family":"Meijers","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., P.E.J.v.d.M., M.A.H.F., N.J.A.M., J.G.-R., J.W.M.H., J.M.E.M.C.); CSL Behring GmbH, Marburg, Germany (F.M.); Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (J.C.M.M.); Department of Plasma Proteins, Sanquin, Amsterdam, The Netherlands (J.C.M.M.); Clinical Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan W.M.","family":"Heemskerk","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., P.E.J.v.d.M., M.A.H.F., N.J.A.M., J.G.-R., J.W.M.H., J.M.E.M.C.); CSL Behring GmbH, Marburg, Germany (F.M.); Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (J.C.M.M.); Department of Plasma Proteins, Sanquin, Amsterdam, The Netherlands (J.C.M.M.); Clinical Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Renn\u00e9","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., P.E.J.v.d.M., M.A.H.F., N.J.A.M., J.G.-R., J.W.M.H., J.M.E.M.C.); CSL Behring GmbH, Marburg, Germany (F.M.); Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (J.C.M.M.); Department of Plasma Proteins, Sanquin, Amsterdam, The Netherlands (J.C.M.M.); Clinical Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith M.E.M.","family":"Cosemans","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., P.E.J.v.d.M., M.A.H.F., N.J.A.M., J.G.-R., J.W.M.H., J.M.E.M.C.); CSL Behring GmbH, Marburg, Germany (F.M.); Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (J.C.M.M.); Department of Plasma Proteins, Sanquin, Amsterdam, The Netherlands (J.C.M.M.); Clinical Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2515"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12045"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050664"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-270918"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.11.001"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2004.12.037"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2748com"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.11.051"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-171066"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20052458"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.109.924761"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-05-355248"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-04-499111"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI103109"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-292094"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11239-011-0578-5"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2008.03186.x"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1080\/10739680701653517"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M000464200"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-368811"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-339572"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvt110"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006804"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-01-266791"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-012-0186-5"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.9.2726"},{"key":"e_1_3_5_28_2","first-page":"451","article-title":"In situ localization of tissue factor in human atherosclerotic plaques by binding of digoxigenin-labeled factors VIIa and X.","volume":"75","author":"Thiruvikraman SV","year":"1996","unstructured":"Thiruvikraman SV, Guha A, Roboz J, Taubman MB, Nemerson Y, Fallon JT. 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