Characterization of a tissue factor/factor VIIa‐dependent model of thrombosis in hypercholesterolemic rabbits
Tissue factor (TF) expressed in arterial atherosclerotic plaque plays a key role in activating the extrinsic coagulation pathway and triggering acute coronary syndromes. In this study, we developed and characterized a TF–factor (F)VIIa‐mediated thrombosis model in rabbits. Balloon catheter‐induced e...
Gespeichert in:
| Veröffentlicht in: | Journal of thrombosis and haemostasis 2004-01, Vol.2 (1), p.85-92 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 92 |
|---|---|
| container_issue | 1 |
| container_start_page | 85 |
| container_title | Journal of thrombosis and haemostasis |
| container_volume | 2 |
| creator | Chi, L. Gibson, G. Peng, Y‐W Bousley, R. Brammer, D. Rekhter, M. Chen, J. Leadley, R. |
| description | Tissue factor (TF) expressed in arterial atherosclerotic plaque plays a key role in activating the extrinsic coagulation pathway and triggering acute coronary syndromes. In this study, we developed and characterized a TF–factor (F)VIIa‐mediated thrombosis model in rabbits. Balloon catheter‐induced endothelial denudation in the femoral artery and a 4‐week high cholesterol diet produced a localized atherosclerotic plaque at the injured site. High levels of TF mRNA and TF protein antigen (152 ± 25 vs. 49 ± 12 pg mg−1 protein in normal vessels) were detected in these atherosclerotic plaques. Plasma FVII coagulant activity (FVII:C) was significantly increased in the hypercholesterolemic rabbits (36 ± 1 s) compared with the normal rabbits (44 ± 1 s, P |
| doi_str_mv | 10.1111/j.1538-7836.2004.00547.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_80097537</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>80097537</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4307-b046ff77f84b6d0db96fdb2205bc7038881f8ddff61513e121e9eed0d5a475cd3</originalsourceid><addsrcrecordid>eNqNkMFOGzEURa0KVAL0Fyqvustgj2fGHqmbKqIkCIlNYGvZ42fF0cw4tSdq0hWfwDfyJXhIKFu8uU96995nHYQwJRlN72qd0ZKJKResynJCioyQsuDZ7gua_F-cvM81Y2foPMY1IbQuc_IVndGCU15zOkF-tlJBNQME908NzvfYW6zw4GLcArZp48PVQfDjYqFenp4NbKA30A-48wbaMTCsgu-0jy5i1-PVfgOhWfkWYupN0rkGB6W1G-IlOrWqjfDtqBfo4ff1cjaf3t3fLGa_7qZNwQifalJU1nJuRaErQ4yuK2t0npNSN5wwIQS1whhrK1pSBjSnUAMkY6kKXjaGXaAfh95N8H-26SOyc7GBtlU9-G2UgpCal4wnozgYm-BjDGDlJrhOhb2kRI6w5VqOHOXIVI6w5RtsuUvR78cbW92B-Qge6SbDz4Phr2th_-liebucp4G9AssCkSo</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>80097537</pqid></control><display><type>article</type><title>Characterization of a tissue factor/factor VIIa‐dependent model of thrombosis in hypercholesterolemic rabbits</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Freely accessible e-journals</source><source>Alma/SFX Local Collection</source><creator>Chi, L. ; Gibson, G. ; Peng, Y‐W ; Bousley, R. ; Brammer, D. ; Rekhter, M. ; Chen, J. ; Leadley, R.</creator><creatorcontrib>Chi, L. ; Gibson, G. ; Peng, Y‐W ; Bousley, R. ; Brammer, D. ; Rekhter, M. ; Chen, J. ; Leadley, R.</creatorcontrib><description>Tissue factor (TF) expressed in arterial atherosclerotic plaque plays a key role in activating the extrinsic coagulation pathway and triggering acute coronary syndromes. In this study, we developed and characterized a TF–factor (F)VIIa‐mediated thrombosis model in rabbits. Balloon catheter‐induced endothelial denudation in the femoral artery and a 4‐week high cholesterol diet produced a localized atherosclerotic plaque at the injured site. High levels of TF mRNA and TF protein antigen (152 ± 25 vs. 49 ± 12 pg mg−1 protein in normal vessels) were detected in these atherosclerotic plaques. Plasma FVII coagulant activity (FVII:C) was significantly increased in the hypercholesterolemic rabbits (36 ± 1 s) compared with the normal rabbits (44 ± 1 s, P < 0.0001). Plaque rupture was induced by balloon angioplasty, which resulted in thrombus formation in the injured vessel segment after a brief period of stasis. FVIIai, a specific TF–FVIIa inhibitor, was administered intravenously to rabbits before plaque rupture at 0.3 and 1.0 mg kg−1. FVIIai dose‐dependently reduced thrombus mass (14.7 ± 2.5 and 5.9 ± 2.2 mg, respectively, vs. 21.6 ± 1.9 mg in the control group). PD198961, a novel factor Xa inhibitor, and argatroban, a thrombin inhibitor, also dose‐dependently inhibited thrombosis. These results indicate that thrombus formation in this model is initiated by the activation of TF–FVIIa pathway, which is attributed to TF expression in the atherosclerotic plaque and enhanced plasma FVII coagulant activity. This model may be useful for evaluating in vivo efficacy of new antithrombotic drugs, particularly TF–FVIIa inhibitors.</description><identifier>ISSN: 1538-7933</identifier><identifier>ISSN: 1538-7836</identifier><identifier>EISSN: 1538-7836</identifier><identifier>DOI: 10.1111/j.1538-7836.2004.00547.x</identifier><identifier>PMID: 14717971</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Inc</publisher><subject>animal model ; Animals ; Arteriosclerosis - blood ; Arteriosclerosis - etiology ; Arteriosclerosis - pathology ; atherosclerotic plaque ; Disease Models, Animal ; Factor VIIa - physiology ; Fibrinolytic Agents - pharmacology ; Gene Expression ; Hypercholesterolemia - blood ; Hypercholesterolemia - complications ; Lipids - blood ; Rabbits ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Thromboplastin - genetics ; Thromboplastin - physiology ; thrombosis ; Thrombosis - blood ; Thrombosis - drug therapy ; Thrombosis - etiology ; Thrombosis - pathology ; tissue factor</subject><ispartof>Journal of thrombosis and haemostasis, 2004-01, Vol.2 (1), p.85-92</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4307-b046ff77f84b6d0db96fdb2205bc7038881f8ddff61513e121e9eed0d5a475cd3</citedby><cites>FETCH-LOGICAL-c4307-b046ff77f84b6d0db96fdb2205bc7038881f8ddff61513e121e9eed0d5a475cd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14717971$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chi, L.</creatorcontrib><creatorcontrib>Gibson, G.</creatorcontrib><creatorcontrib>Peng, Y‐W</creatorcontrib><creatorcontrib>Bousley, R.</creatorcontrib><creatorcontrib>Brammer, D.</creatorcontrib><creatorcontrib>Rekhter, M.</creatorcontrib><creatorcontrib>Chen, J.</creatorcontrib><creatorcontrib>Leadley, R.</creatorcontrib><title>Characterization of a tissue factor/factor VIIa‐dependent model of thrombosis in hypercholesterolemic rabbits</title><title>Journal of thrombosis and haemostasis</title><addtitle>J Thromb Haemost</addtitle><description>Tissue factor (TF) expressed in arterial atherosclerotic plaque plays a key role in activating the extrinsic coagulation pathway and triggering acute coronary syndromes. In this study, we developed and characterized a TF–factor (F)VIIa‐mediated thrombosis model in rabbits. Balloon catheter‐induced endothelial denudation in the femoral artery and a 4‐week high cholesterol diet produced a localized atherosclerotic plaque at the injured site. High levels of TF mRNA and TF protein antigen (152 ± 25 vs. 49 ± 12 pg mg−1 protein in normal vessels) were detected in these atherosclerotic plaques. Plasma FVII coagulant activity (FVII:C) was significantly increased in the hypercholesterolemic rabbits (36 ± 1 s) compared with the normal rabbits (44 ± 1 s, P < 0.0001). Plaque rupture was induced by balloon angioplasty, which resulted in thrombus formation in the injured vessel segment after a brief period of stasis. FVIIai, a specific TF–FVIIa inhibitor, was administered intravenously to rabbits before plaque rupture at 0.3 and 1.0 mg kg−1. FVIIai dose‐dependently reduced thrombus mass (14.7 ± 2.5 and 5.9 ± 2.2 mg, respectively, vs. 21.6 ± 1.9 mg in the control group). PD198961, a novel factor Xa inhibitor, and argatroban, a thrombin inhibitor, also dose‐dependently inhibited thrombosis. These results indicate that thrombus formation in this model is initiated by the activation of TF–FVIIa pathway, which is attributed to TF expression in the atherosclerotic plaque and enhanced plasma FVII coagulant activity. This model may be useful for evaluating in vivo efficacy of new antithrombotic drugs, particularly TF–FVIIa inhibitors.</description><subject>animal model</subject><subject>Animals</subject><subject>Arteriosclerosis - blood</subject><subject>Arteriosclerosis - etiology</subject><subject>Arteriosclerosis - pathology</subject><subject>atherosclerotic plaque</subject><subject>Disease Models, Animal</subject><subject>Factor VIIa - physiology</subject><subject>Fibrinolytic Agents - pharmacology</subject><subject>Gene Expression</subject><subject>Hypercholesterolemia - blood</subject><subject>Hypercholesterolemia - complications</subject><subject>Lipids - blood</subject><subject>Rabbits</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Thromboplastin - genetics</subject><subject>Thromboplastin - physiology</subject><subject>thrombosis</subject><subject>Thrombosis - blood</subject><subject>Thrombosis - drug therapy</subject><subject>Thrombosis - etiology</subject><subject>Thrombosis - pathology</subject><subject>tissue factor</subject><issn>1538-7933</issn><issn>1538-7836</issn><issn>1538-7836</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkMFOGzEURa0KVAL0Fyqvustgj2fGHqmbKqIkCIlNYGvZ42fF0cw4tSdq0hWfwDfyJXhIKFu8uU96995nHYQwJRlN72qd0ZKJKResynJCioyQsuDZ7gua_F-cvM81Y2foPMY1IbQuc_IVndGCU15zOkF-tlJBNQME908NzvfYW6zw4GLcArZp48PVQfDjYqFenp4NbKA30A-48wbaMTCsgu-0jy5i1-PVfgOhWfkWYupN0rkGB6W1G-IlOrWqjfDtqBfo4ff1cjaf3t3fLGa_7qZNwQifalJU1nJuRaErQ4yuK2t0npNSN5wwIQS1whhrK1pSBjSnUAMkY6kKXjaGXaAfh95N8H-26SOyc7GBtlU9-G2UgpCal4wnozgYm-BjDGDlJrhOhb2kRI6w5VqOHOXIVI6w5RtsuUvR78cbW92B-Qge6SbDz4Phr2th_-liebucp4G9AssCkSo</recordid><startdate>200401</startdate><enddate>200401</enddate><creator>Chi, L.</creator><creator>Gibson, G.</creator><creator>Peng, Y‐W</creator><creator>Bousley, R.</creator><creator>Brammer, D.</creator><creator>Rekhter, M.</creator><creator>Chen, J.</creator><creator>Leadley, R.</creator><general>Blackwell Science Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200401</creationdate><title>Characterization of a tissue factor/factor VIIa‐dependent model of thrombosis in hypercholesterolemic rabbits</title><author>Chi, L. ; Gibson, G. ; Peng, Y‐W ; Bousley, R. ; Brammer, D. ; Rekhter, M. ; Chen, J. ; Leadley, R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4307-b046ff77f84b6d0db96fdb2205bc7038881f8ddff61513e121e9eed0d5a475cd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>animal model</topic><topic>Animals</topic><topic>Arteriosclerosis - blood</topic><topic>Arteriosclerosis - etiology</topic><topic>Arteriosclerosis - pathology</topic><topic>atherosclerotic plaque</topic><topic>Disease Models, Animal</topic><topic>Factor VIIa - physiology</topic><topic>Fibrinolytic Agents - pharmacology</topic><topic>Gene Expression</topic><topic>Hypercholesterolemia - blood</topic><topic>Hypercholesterolemia - complications</topic><topic>Lipids - blood</topic><topic>Rabbits</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Thromboplastin - genetics</topic><topic>Thromboplastin - physiology</topic><topic>thrombosis</topic><topic>Thrombosis - blood</topic><topic>Thrombosis - drug therapy</topic><topic>Thrombosis - etiology</topic><topic>Thrombosis - pathology</topic><topic>tissue factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chi, L.</creatorcontrib><creatorcontrib>Gibson, G.</creatorcontrib><creatorcontrib>Peng, Y‐W</creatorcontrib><creatorcontrib>Bousley, R.</creatorcontrib><creatorcontrib>Brammer, D.</creatorcontrib><creatorcontrib>Rekhter, M.</creatorcontrib><creatorcontrib>Chen, J.</creatorcontrib><creatorcontrib>Leadley, R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of thrombosis and haemostasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chi, L.</au><au>Gibson, G.</au><au>Peng, Y‐W</au><au>Bousley, R.</au><au>Brammer, D.</au><au>Rekhter, M.</au><au>Chen, J.</au><au>Leadley, R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of a tissue factor/factor VIIa‐dependent model of thrombosis in hypercholesterolemic rabbits</atitle><jtitle>Journal of thrombosis and haemostasis</jtitle><addtitle>J Thromb Haemost</addtitle><date>2004-01</date><risdate>2004</risdate><volume>2</volume><issue>1</issue><spage>85</spage><epage>92</epage><pages>85-92</pages><issn>1538-7933</issn><issn>1538-7836</issn><eissn>1538-7836</eissn><abstract>Tissue factor (TF) expressed in arterial atherosclerotic plaque plays a key role in activating the extrinsic coagulation pathway and triggering acute coronary syndromes. In this study, we developed and characterized a TF–factor (F)VIIa‐mediated thrombosis model in rabbits. Balloon catheter‐induced endothelial denudation in the femoral artery and a 4‐week high cholesterol diet produced a localized atherosclerotic plaque at the injured site. High levels of TF mRNA and TF protein antigen (152 ± 25 vs. 49 ± 12 pg mg−1 protein in normal vessels) were detected in these atherosclerotic plaques. Plasma FVII coagulant activity (FVII:C) was significantly increased in the hypercholesterolemic rabbits (36 ± 1 s) compared with the normal rabbits (44 ± 1 s, P < 0.0001). Plaque rupture was induced by balloon angioplasty, which resulted in thrombus formation in the injured vessel segment after a brief period of stasis. FVIIai, a specific TF–FVIIa inhibitor, was administered intravenously to rabbits before plaque rupture at 0.3 and 1.0 mg kg−1. FVIIai dose‐dependently reduced thrombus mass (14.7 ± 2.5 and 5.9 ± 2.2 mg, respectively, vs. 21.6 ± 1.9 mg in the control group). PD198961, a novel factor Xa inhibitor, and argatroban, a thrombin inhibitor, also dose‐dependently inhibited thrombosis. These results indicate that thrombus formation in this model is initiated by the activation of TF–FVIIa pathway, which is attributed to TF expression in the atherosclerotic plaque and enhanced plasma FVII coagulant activity. This model may be useful for evaluating in vivo efficacy of new antithrombotic drugs, particularly TF–FVIIa inhibitors.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Inc</pub><pmid>14717971</pmid><doi>10.1111/j.1538-7836.2004.00547.x</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1538-7933 |
| ispartof | Journal of thrombosis and haemostasis, 2004-01, Vol.2 (1), p.85-92 |
| issn | 1538-7933 1538-7836 1538-7836 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_80097537 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Freely accessible e-journals; Alma/SFX Local Collection |
| subjects | animal model Animals Arteriosclerosis - blood Arteriosclerosis - etiology Arteriosclerosis - pathology atherosclerotic plaque Disease Models, Animal Factor VIIa - physiology Fibrinolytic Agents - pharmacology Gene Expression Hypercholesterolemia - blood Hypercholesterolemia - complications Lipids - blood Rabbits RNA, Messenger - genetics RNA, Messenger - metabolism Thromboplastin - genetics Thromboplastin - physiology thrombosis Thrombosis - blood Thrombosis - drug therapy Thrombosis - etiology Thrombosis - pathology tissue factor |
| title | Characterization of a tissue factor/factor VIIa‐dependent model of thrombosis in hypercholesterolemic rabbits |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-14T13%3A58%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Characterization%20of%20a%20tissue%20factor/factor%20VIIa%E2%80%90dependent%20model%20of%20thrombosis%20in%20hypercholesterolemic%20rabbits&rft.jtitle=Journal%20of%20thrombosis%20and%20haemostasis&rft.au=Chi,%20L.&rft.date=2004-01&rft.volume=2&rft.issue=1&rft.spage=85&rft.epage=92&rft.pages=85-92&rft.issn=1538-7933&rft.eissn=1538-7836&rft_id=info:doi/10.1111/j.1538-7836.2004.00547.x&rft_dat=%3Cproquest_cross%3E80097537%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=80097537&rft_id=info:pmid/14717971&rfr_iscdi=true |