| Hirudin reduces tissue factor expression in neointima after balloon injury in rabbit femoral and porcine coronary arteries. | |
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MedLine Citation:
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PMID: 9714116 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Tissue factor (TF) is a transmembrane glycoprotein that, after binding to factor VII/VIIa, initiates the extrinsic coagulation pathway, resulting in thrombin generation and its sequelae. Thrombin has been shown to induce TF mRNA in endothelium, monocytes, and smooth muscle cells, further perpetuating the thrombogenic cycle. This study was designed to determine the effect of specific inhibition of thrombin by recombinant hirudin (r-hirudin) on TF distribution after balloon angioplasty in the cholesterol-fed rabbit femoral artery and porcine coronary artery models. METHODS AND RESULTS: Thirty-five femoral arteries from 32 cholesterol-fed New Zealand White rabbits and 84 coronary arteries from 55 Yorkshire-Albino swine were studied by use of a recently developed in situ method of TF localization based on digoxigenin labeling of recombinant factor VIIa (Dig-VIIa), with correlative studies of TF immunoreactivity by use of anti-rabbit (AP-1) or anti-human (sTF) antibodies. At sites of balloon angioplasty in rabbit femoral or pig coronary arteries (double or single injury), TF-antibody and Dig-VIIa staining were noted in association with endothelial cells, smooth muscle cells, and foam cells and within the fibrous tissue matrix primarily of the adventitia and neointima. Staining was significantly greater after balloon angioplasty than in vessels that had not undergone angioplasty but was similar after single and double balloon injury. Animals treated with r-hirudin (rabbits, 1 mg/kg bolus plus 2-hour infusion; pigs, 1 mg/kg bolus plus 0.7 mg x kg(-1) x d(-1) infusion for 14 days with implantable pump) had diminished TF-antibody and Dig-VIIa staining 28 days after balloon angioplasty compared with controls (bolus heparin only). This effect was more prominent on the neointima and was more striking in the porcine than the rabbit model. CONCLUSIONS: TF expression, persistent 1 month after balloon angioplasty in rabbit femoral arteries and porcine coronary arteries, is attenuated by specific thrombin inhibition with hirudin. These results suggest that thrombin inhibition, in addition to its effect on acute thrombus formation and its effect on luminal narrowing by plaque in experimental animals, may result in a prolonged reduction in thrombogenicity of the restenotic plaque through this effect on TF expression. |
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Authors:
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S D Gertz; J T Fallon; R Gallo; M B Taubman; S Banai; W L Barry; L W Gimple; Y Nemerson; S Thiruvikraman; S S Naidu; J H Chesebro; V Fuster; I J Sarembock; J J Badimon |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Circulation Volume: 98 ISSN: 0009-7322 ISO Abbreviation: Circulation Publication Date: 1998 Aug |
Date Detail:
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Created Date: 1998-09-15 Completed Date: 1998-09-15 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 580-7 Citation Subset: AIM; IM |
Affiliation:
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Department of Anatomy and Cell Biology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel. gertz@cc.huji.ac.il |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angioplasty, Balloon
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adverse effects* Animals Cholesterol, Dietary / administration & dosage Coronary Vessels / injuries*, metabolism, pathology Digoxigenin Factor VIIa / metabolism Femoral Artery / injuries*, metabolism, pathology Hirudins / pharmacology* Male Rabbits Recombinant Proteins Swine Thrombin / antagonists & inhibitors Thromboplastin / metabolism* Tunica Intima / metabolism* Wounds and Injuries / pathology |
| Grant Support | |
ID/Acronym/Agency:
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R01-HL-7849/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cholesterol, Dietary; 0/Hirudins; 0/Recombinant Proteins; 1672-46-4/Digoxigenin; 9035-58-9/Thromboplastin; EC 3.4.21.21/Factor VIIa; EC 3.4.21.5/Thrombin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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