Show simple item record

dc.contributor.authorKranzhöfer, Roger
dc.contributor.authorMaraganore, John M.
dc.contributor.authorBaciu, Rem
dc.contributor.authorLibby, Peter
dc.date.accessioned2018-03-27T18:41:37Z
dc.date.issued1999
dc.identifier.citationKranzhöfer, Roger, John M. Maraganore, Rem Baciu, and Peter Libby. 1999. "Systemic Thrombin Inhibition by Hirulog Does Not Alter Medial Smooth Muscle Cell Proliferation and Inflammatory Activation after Vascular Injury in the Rabbit." Cardiovascular Drugs and Therapy 13, no. 5: 429–434. doi:10.1023/A:1007808123953en_US
dc.identifier.issn0920-3206en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:35140998
dc.description.abstractSummary. The study evaluated the role of thrombin in activation of vascular smooth muscle cells early after vascular injury. The direct thrombin inhibitor Hirulog (10 mg/kg SQ tid) or vehicle was administered to rabbits over 3 days following balloon injury to the abdominal aorta and the right iliac artery. Hirulog treatment yielded marked systemic anticoagulation as evidenced by an about 3.5-fold prolongation of quantitative thrombin time one hour after an injection, but with a reduction to almost baseline levels at the end of the dosing interval. After 3 days, proliferating cells in the right iliac artery were enumerated. The expression of intercellular adhesion molecule 1, macrophage-colony stimulating factor, tumor necrosis factor α, and interleukin-1β as markers for inflammatory activation of the vessel wall was examined by immunohistochemistry and graded semiquantitatively. Mitotic indices did not differ between control and Hirulog-treated animals. There was also no difference in the expression of markers of inflammatory activation between both groups. In conclusion, thrombin inhibition by Hirulog administration does not reduce acutely (within 3 days) vascular smooth muscle cell proliferation or inflammatory activation after angioplasty. Thrombin inhibitors may therefore limit restenosis in the rabbit by acting later or via other, unknown pathways. The lack of effect of the thrombin inhibitor on the cellular events during the early phase of the response to balloon injury may explain the failure of such strategies to reduce restenosis in recent clinical trials despite effects towards acute thrombotic complications. Together, these results suggest that acute thrombin generation is not a crucial stimulus for early smooth muscle cell proliferation and inflammatory activation after vascular injury.en_US
dc.language.isoen_USen_US
dc.publisherSpringer Science + Business Mediaen_US
dc.relation.isversionofdoi:10.1023/A:1007808123953en_US
dash.licenseMETA_ONLY
dc.subjectthrombinen_US
dc.subjectsmooth muscle cellsen_US
dc.subjectinflammationen_US
dc.subjectproliferationen_US
dc.subjectarteriosclerosisen_US
dc.subjectrestenosisen_US
dc.titleSystemic Thrombin Inhibition by Hirulog Does Not Alter Medial Smooth Muscle Cell Proliferation and Inflammatory Activation after Vascular Injury in the Rabbiten_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalCardiovascular Drugs and Therapyen_US
dash.depositing.authorLibby, Peter
dash.embargo.until10000-01-01
dc.identifier.doi10.1023/A:1007808123953*
workflow.legacycommentsnoap.needmanen_US
dash.contributor.affiliatedLibby, Peter


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record