| Thrombin inhibitor reduces myocardial infarction in apoE-/- x LDLR-/- mice. | |
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MedLine Citation:
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PMID: 15031124 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have previously shown that atherosclerotic apolipoprotein E-deficient (apoE(-/-)) x LDL receptor-deficient (LDLR(-/-)) mice develop myocardial infarction when exposed to hypoxic stress. This study was performed to assess the role of thrombin and thrombosis in this process. ApoE(-/-) x LDLR(-/-) mice were fed a cholesterol-rich diet for 8 mo and were then subjected to hypoxic stress while receiving isoflurane anesthesia. One group received a bolus dose (5.6 micromol/kg) of the thrombin inhibitor melagatran, and control animals received PBS 10 min before the hypoxic stress. The mice were exposed to 10 min of hypoxia followed by normoxia. Ten minutes after the stress, Alzet pumps delivering melagatran (20 nmol x kg x (-1)min(-1)) or PBS were implanted, and the mice were allowed to recover for 48 h. The cardiac response was analyzed by histology, immunohistochemistry, and serum troponin T assay. All animals showed reversible ECG changes as a sign of ischemia during hypoxic stress, and 50% developed infarctions afterward as judged by troponin T levels. The group that received thrombin inhibitor had significantly lower troponin T and smaller myocardial infarctions than the PBS-treated group. These data show that thrombin generation is an important pathogenetic factor and suggest that coronary thrombosis is involved in myocardial infarction in atherosclerotic mice. Exposure of atherosclerotic mice to hypoxia leads to myocardial infarction through a two-phase pathway in which acute transient ischemia is followed by thrombin-dependent, irreversible, myocardial ischemia and myocardial cell death. |
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Authors:
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Anne-Louise Hemdahl; Erling Falk; Peter Thorén; Göran K Hansson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2004-03-18 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 287 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2004 Aug |
Date Detail:
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Created Date: 2004-07-27 Completed Date: 2004-09-03 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H872-7 Citation Subset: IM |
Affiliation:
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Department of Medicine, Karolinska Institute, SE-171 76, Stockholm, Sweden. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apolipoproteins E / deficiency* Azetidines Benzylamines Biological Markers / analysis Coronary Artery Disease / metabolism, pathology Coronary Thrombosis / metabolism, pathology Electrocardiography Glycine / analogs & derivatives*, pharmacology* Male Mice Mice, Inbred C57BL Mice, Knockout Myocardial Infarction / diagnosis, metabolism, pathology* Myocardium / metabolism, pathology Receptors, LDL / deficiency* Thrombin / antagonists & inhibitors* Troponin T / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Apolipoproteins E; 0/Azetidines; 0/Benzylamines; 0/Biological Markers; 0/Receptors, LDL; 0/Troponin T; 159776-70-2/melagatran; 56-40-6/Glycine; EC 3.4.21.5/Thrombin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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