| Cellular and molecular mechanism regulating blood flow recovery in acute versus gradual femoral artery occlusion are distinct in the mouse. | |
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MedLine Citation:
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PMID: 19118738 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Most current animal models of hindlimb ischemia use acute arterial occlusion that does not accurately reflect the pathogenesis of gradual arterial occlusion in humans. We, therefore, developed the first mouse model of gradual arterial occlusion and tested the hypothesis that the mechanisms regulating blood flow recovery are critically dependent on the rate of arterial occlusion. METHODS: Gradual arterial occlusion was induced by placing ameroid constrictors on the proximal and distal left femoral artery, and ligating the femoral arterial branches (n = 36). Acute arterial occlusion was accomplished by excising the left femoral artery (n = 36). The blood flow recovery was studied by laser Doppler imaging. Differential gene expression between these two models was assessed by quantitative real-time polymerase chain reactions (PCR). Inflammatory and progenitor cells recruitment were determined by immunohistochemistry. RESULTS: We found that hypoxia-related genes increased significantly in the calf, but not in the thigh, after gradual and acute femoral arterial occlusion (P < .05). Shear-stress dependent genes and inflammatory genes were upregulated immediately in the thigh only after acute femoral arterial occlusion (P < .05). These differences in gene expression were consistent with increased SDF-1alpha expression, recruitment of macrophages and hemangiocytes, and higher blood flow recovery after acute arterial occlusion than after gradual arterial occlusion (P < .05). CONCLUSION: This is the first study to show the mechanisms that regulate blood flow recovery are critically dependent on the rate of arterial occlusion. This novel model of gradual arterial occlusion may more closely resemble the human diseases, and may provide more accurate mechanistic insights for creating novel molecular therapies. |
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Authors:
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Yagai Yang; Gale Tang; Jinglian Yan; Brian Park; Ari Hoffman; Guodong Tie; Rong Wang; Louis M Messina |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of vascular surgery : official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter Volume: 48 ISSN: 1097-6809 ISO Abbreviation: J. Vasc. Surg. Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2009-01-02 Completed Date: 2009-01-22 Revised Date: 2010-09-22 |
Medline Journal Info:
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Nlm Unique ID: 8407742 Medline TA: J Vasc Surg Country: United States |
Other Details:
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Languages: eng Pagination: 1546-58 Citation Subset: IM |
Affiliation:
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Department of Medicine, Division of Cardiology, University of California, San Francisco, California, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acute Disease Animals Arterial Occlusive Diseases / genetics, metabolism, physiopathology* Blood Flow Velocity / physiology* Chemokine CXCL12 / biosynthesis, genetics* Chronic Disease Disease Models, Animal Disease Progression Endothelium, Vascular / metabolism, pathology Femoral Artery / physiology* Gene Expression* Immunohistochemistry Laser-Doppler Flowmetry Mice Mice, Inbred C57BL Muscle, Skeletal / metabolism, pathology Polymerase Chain Reaction RNA, Messenger / genetics* Recovery of Function / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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HL75353/HL/NHLBI NIH HHS; R01 HL075353-04/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chemokine CXCL12; 0/RNA, Messenger |
| Comments/Corrections | |
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