{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:45:15Z","timestamp":1773661515733,"version":"3.50.1"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[1999,3]]},"abstract":"<jats:p>\n            <jats:italic>Background and Purpose<\/jats:italic>\n            \u2014Activation of plasma protein C (PC) zymogen by thrombin-thrombomodulin at the endothelial surface is an important endogenous antithrombotic mechanism. It is unknown whether activated protein C (APC) is generated in vivo in the cerebrovasculature, because there is only limited thrombomodulin expression in human brain vascular endothelium. Therefore, we tested the hypothesis that carotid occlusion produces brain-specific PC activation.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods<\/jats:italic>\n            \u2014Blood samples were simultaneously collected from the ipsilateral internal jugular vein and radial artery before and during carotid cross-clamping and on \u201cde-occlusion\u201d in 8 awake patients undergoing routine carotid endarterectomy. Plasma PC zymogen and circulating APC levels were measured using enzyme immunocapture assay and expressed as percent of pooled plasma controls.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Results<\/jats:italic>\n            \u2014Internal jugular vein APC levels increased 28% exclusively during carotid occlusion and then decreased 32% with de-occlusion (F=8.1,\n            <jats:italic>P<\/jats:italic>\n            &lt;0.005). PC zymogen increased only 5.9% with occlusion (F=6.3,\n            <jats:italic>P<\/jats:italic>\n            &lt;0.02), consistent with hemoconcentration. There were no changes in radial artery PC or APC levels.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014These findings demonstrate brain-specific protein C activation in humans during carotid occlusion and suggest a protective role for endogenous APC generation during cerebrovascular occlusion.\n          <\/jats:p>","DOI":"10.1161\/01.str.30.3.542","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T20:08:03Z","timestamp":1308341283000},"page":"542-545","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["Brain-Specific Protein C Activation During Carotid Artery Occlusion in Humans"],"prefix":"10.1161","volume":"30","author":[{"given":"Richard F.","family":"Macko","sequence":"first","affiliation":[{"name":"From the Departments of Neurology (R.F.M., D.K.C.) and Surgery (L.A.K.) and the Geriatrics Research Education and Clinical Center (R.F.M.), Baltimore Department of Veterans Affairs Medical Center, University of Maryland School of Medicine, Baltimore,, and the Departments of Molecular and Experimental Medicine and Vascular Biology (J.A.F., A.G., J.H.G.), The Scripps Research Institute, La Jolla, Calif."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lois A.","family":"Killewich","sequence":"additional","affiliation":[{"name":"From the Departments of Neurology (R.F.M., D.K.C.) and Surgery (L.A.K.) and the Geriatrics Research Education and Clinical Center (R.F.M.), Baltimore Department of Veterans Affairs Medical Center, University of Maryland School of Medicine, Baltimore,, and the Departments of Molecular and Experimental Medicine and Vascular Biology (J.A.F., A.G., J.H.G.), The Scripps Research Institute, La Jolla, Calif."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose\u0301 A.","family":"Ferna\u0301ndez","sequence":"additional","affiliation":[{"name":"From the Departments of Neurology (R.F.M., D.K.C.) and Surgery (L.A.K.) and the Geriatrics Research Education and Clinical Center (R.F.M.), Baltimore Department of Veterans Affairs Medical Center, University of Maryland School of Medicine, Baltimore,, and the Departments of Molecular and Experimental Medicine and Vascular Biology (J.A.F., A.G., J.H.G.), The Scripps Research Institute, La Jolla, Calif."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. Kim","family":"Cox","sequence":"additional","affiliation":[{"name":"From the Departments of Neurology (R.F.M., D.K.C.) and Surgery (L.A.K.) and the Geriatrics Research Education and Clinical Center (R.F.M.), Baltimore Department of Veterans Affairs Medical Center, University of Maryland School of Medicine, Baltimore,, and the Departments of Molecular and Experimental Medicine and Vascular Biology (J.A.F., A.G., J.H.G.), The Scripps Research Institute, La Jolla, Calif."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andras","family":"Gruber","sequence":"additional","affiliation":[{"name":"From the Departments of Neurology (R.F.M., D.K.C.) and Surgery (L.A.K.) and the Geriatrics Research Education and Clinical Center (R.F.M.), Baltimore Department of Veterans Affairs Medical Center, University of Maryland School of Medicine, Baltimore,, and the Departments of Molecular and Experimental Medicine and Vascular Biology (J.A.F., A.G., J.H.G.), The Scripps Research Institute, La Jolla, Calif."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John H.","family":"Griffin","sequence":"additional","affiliation":[{"name":"From the Departments of Neurology (R.F.M., D.K.C.) and Surgery (L.A.K.) and the Geriatrics Research Education and Clinical Center (R.F.M.), Baltimore Department of Veterans Affairs Medical Center, University of Maryland School of Medicine, Baltimore,, and the Departments of Molecular and Experimental Medicine and Vascular Biology (J.A.F., A.G., J.H.G.), The Scripps Research Institute, La Jolla, Calif."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.19.5.3363590"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.27.11.2005"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V62.6.1155.1155"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V67.2.362.362"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)90540-C"},{"key":"e_1_3_2_6_2","first-page":"423","volume":"33","year":"1991","unstructured":"Boffa MC, Jackman RW, Peyri N, George B. Thrombomodulin in the central nervous system. Nouv Rev Fr Hematol. 1991;33:423\u2013429.","journal-title":"Nouv Rev Fr Hematol"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01306457"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.27.12.2304"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V79.9.2340.2340"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1992.45"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8652(199709)56:1<29::AID-AJH6>3.0.CO;2-4"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.4.1159.1159"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116795"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.82.2.2372904"},{"key":"e_1_3_2_15_2","first-page":"258a","volume":"90","year":"1997","unstructured":"Jalbert LR, Rosen ED, Carmeliet P, Castellino FJ, Collen D. Characterization of the anticoagulant protein C by targeted inactivation in mice. Blood. 1997;90:258a. Abstract.","journal-title":"Blood"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.84.1.2060102"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.90.1.8026029"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112902"},{"key":"e_1_3_2_19_2","first-page":"523","volume":"118","year":"1991","unstructured":"Krishnamurti C, Young GD, Barr CF, Curtis A, Colleton CA, Alving BM. Enhancement of tissue plasminogen activator-induced fibrinolysis by activated protein C in endotoxin-treated rabbits. J Lab Clin Med. 1991;118:523\u2013530.","journal-title":"J Lab Clin Med"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830330413"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.153.8.3664"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.156.6.2256"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1646385"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.28.6.1233"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410320113"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1642492"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.30.4.350"},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"16303","DOI":"10.1016\/S0021-9258(18)71622-0","volume":"264","year":"1989","unstructured":"Haley PE, Doyle MF, Mann KG. The activation of bovine protein C by factor Xa. J Biol Chem. 1989;264:16303\u201316310.","journal-title":"J Biol Chem"},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"4572","DOI":"10.1182\/blood.V91.12.4572","volume":"91","year":"1998","unstructured":"Rezaie AR. Rapid activation of protein C by factor Xa and thrombin in the presence of polyanionic compounds. Blood. 1998;91:4572\u20134580.","journal-title":"Blood"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2610341"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1973.01350160134022"},{"key":"e_1_3_2_32_2","unstructured":"Toole JF. Anatomy and diseases of the venous system. In: Cerebrovascular Disorders. 4th ed. New York NY: Raven Press Publishers; 1990:503\u2013518."},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.43.25336"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.19.10212"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-125-4-199608150-00002"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.27.7.1163"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199710303371812"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115514"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.eurheartj.a014713"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.17.11.3139"},{"key":"e_1_3_2_41_2","first-page":"286","volume":"29","year":"1998","unstructured":"Macko RF, Kittner SJ, Refsum H, Cox D, Epstein A, Sparks M, Johnson C, Wityk R, Ueland P. Effects of vitamin therapy on plasma homocysteine, endogenous fibrinolysis, and markers of endothelial injury in stroke patients: a placebo-controlled trial. Stroke. 1998;29:286. Abstract.","journal-title":"Stroke"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.STR.30.3.542","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T22:02:45Z","timestamp":1715551365000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.STR.30.3.542"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,3]]},"references-count":41,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1999,3]]}},"alternative-id":["10.1161\/01.STR.30.3.542"],"URL":"https:\/\/doi.org\/10.1161\/01.str.30.3.542","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,3]]},"assertion":[{"value":"1998-08-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-12-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-03-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}