Document Detail


Expression of hypoxia-inducible angiogenic proteins (hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and E26 transformation-specific-1) and plaque hemorrhage in human carotid atherosclerosis.
MedLine Citation:
PMID:  18590436     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECT: Plaque hemorrhage in carotid atherosclerosis promotes plaque progression, resulting in cerebrovascular disease. Hypoxia inducible factor-1alpha (HIF-1alpha) induces angiogenesis via the expression of vascular endothelial growth factor (VEGF) and E26 transformation-specific-1 (Ets-1). The authors investigated human carotid plaques to determine whether these hypoxia-inducible angiogenic proteins play a major role in intraplaque angiogenesis and hemorrhage. METHODS: The expression of HIF-1alpha, VEGF, and Ets-1 was analyzed using immunohistochemistry and Western blotting in 29 human carotid plaques obtained at carotid endarterectomy. The authors investigated the relationship between plaque characteristics and clinical symptoms. RESULTS: A higher incidence of plaque hemorrhage was observed in plaques associated with symptoms than in those without symptoms (p = 0.03). Hypoxia-inducible factor-1alpha, VEGF, and Ets-1 coexisted in the deep layer of plaque, where angiogenesis was remarkably developed; the expression levels of HIF-1alpha, VEGF, and Ets-1 were significantly enhanced in the main lesion of the plaque (p < 0.01). Symptomatic plaques showed higher expression of VEGF (p = 0.04) than asymptomatic plaques. Plaques with hemorrhage showed a higher incidence of plaque ulcer (p = 0.001) and higher expression of Ets-1 (p = 0.03) than those without hemorrhage. Moreover, significantly increased expressions of VEGF (p = 0.01) and Ets-1 (p = 0.006) were observed in plaques with not only hemorrhages but also ulcers and severe stenosis. CONCLUSIONS: The findings in this study suggest that hypoxia-inducible angiogenic proteins in human carotid atherosclerosis promote intraplaque angiogenesis, which can induce plaque hemorrhage and progression.
Authors:
Tetsuhiro Higashida; Hiroshi Kanno; Masato Nakano; Kengo Funakoshi; Isao Yamamoto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurosurgery     Volume:  109     ISSN:  0022-3085     ISO Abbreviation:  J. Neurosurg.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-01     Completed Date:  2008-07-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0253357     Medline TA:  J Neurosurg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  83-91     Citation Subset:  AIM; IM    
Affiliation:
Department of Neurosurgery, Yokohama City University, Yokohama, Japan. t056042a@yokohama-cu.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Aged
Atherosclerosis / complications,  metabolism*,  pathology
Carotid Artery Diseases / complications,  metabolism*,  pathology
Case-Control Studies
Cohort Studies
Female
Hemorrhage / etiology*,  metabolism,  pathology
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
Male
Middle Aged
Neovascularization, Pathologic / complications,  metabolism,  pathology
Proto-Oncogene Protein c-ets-1 / metabolism*
Vascular Endothelial Growth Factor A / metabolism*
Chemical
Reg. No./Substance:
0/ETS1 protein, human; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Proto-Oncogene Protein c-ets-1; 0/Vascular Endothelial Growth Factor A

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