Document Detail

Nonischemic cerebral venous hypertension promotes a pro-angiogenic stage through HIF-1 downstream genes and leukocyte-derived MMP-9.
MedLine Citation:
PMID:  19471278     Owner:  NLM     Status:  MEDLINE    
Cerebral venous hypertension (VH) and angiogenesis are implicated in the pathogenesis of brain arteriovenous malformation and dural arteriovenous fistulae. We studied the association of VH and angiogenesis using a mouse brain VH model. Sixty mice underwent external jugular vein and common carotid artery (CCA) anastomosis (VH model), CCA ligation, or sham dissection (n=20). Hypoxia-inducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF) and stromal-cell-derived factor-1alpha (SDF-1alpha) expression, and matrix metalloproteinase (MMP) activity were analyzed. We found VH animals had higher (P<0.05) sagittal sinus pressure (8+/-1 mm Hg) than control groups (1+/-1 mm Hg). Surface cerebral blood flow and mean arterial pressure did not change. Hypoxia-inducible factor-1alpha, VEGF, and SDF-1alpha expression increased (P<0.05). Neutrophils and MMP-9 activity increased 10-fold 1 day after surgery, gradually decreased afterward, and returned to baseline 2 weeks after surgery. Macrophages began to increase 3 days after surgery (P<0.05), which coincided with the changes in SDF-1alpha expression. Capillary density in the parasagittal cortex increased 17% compared with the controls. Our findings suggest that mild nonischemic VH results in a pro-angiogenic stage in the brain by upregulating HIF-1 and its downstream targets, VEGF and SDF-1alpha, increasing leukocyte infiltration and MMP-9 activity.
Peng Gao; Yiqian Zhu; Feng Ling; Fanxia Shen; Brian Lee; Rodney Allanigue Gabriel; Qi Hao; Guo-Yuan Yang; Hua Su; William L Young
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-05-27
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  29     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-07-31     Completed Date:  2009-08-13     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1482-90     Citation Subset:  IM    
Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California, San Francisco, California 94110, USA.
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MeSH Terms
Blood Flow Velocity / physiology
Blotting, Western
Cerebral Veins / metabolism,  pathology*
Cerebrovascular Circulation / physiology
Chemokine CXCL12 / biosynthesis,  genetics
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Gene Expression Regulation / drug effects*
Hypertension / genetics,  metabolism,  pathology*
Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis*
Macrophages / pathology
Matrix Metalloproteinase 9 / biosynthesis*,  genetics
Mice, Inbred C57BL
Neovascularization, Pathologic / enzymology,  genetics*,  metabolism,  pathology
Neutrophil Infiltration
Neutrophils / enzymology*
Vascular Endothelial Growth Factor A / biosynthesis,  genetics
Grant Support
Reg. No./Substance:
0/Chemokine CXCL12; 0/Hif1a protein, mouse; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Vascular Endothelial Growth Factor A; 0/vascular endothelial growth factor A, mouse; EC Metalloproteinase 9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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