Document Detail


Angiostatin is negatively associated with coronary collateral growth in patients with coronary artery disease.
MedLine Citation:
PMID:  15840902     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Angiostatin, an inhibitor of tumor angiogenesis, is produced by the actions of matrix metalloproteinases (MMP) on plasminogen. Recently, we reported that angiostatin levels are increased in a model of inadequate coronary collateral growth and angiogenesis in response to ischemia, despite high levels of vascular endothelial growth factor (VEGF). We hypothesized that angiostatin levels are negatively associated with collateral formation in patients. Coronary angiograms from 37 patients undergoing coronary bypass surgery were evaluated for the absence of angiographically visible collaterals (Rentrop scores of 0) or the presence of Rentrop classification grade 3 (well developed) collaterals. Pericardial fluid was obtained from each patient during the bypass procedure, and the sample was analyzed for angiostatin, plasminogen, and VEGF (Western analysis) and for combined activities of MMP-2 and MMP-9 (zymographic analysis). In patients with no collaterals, angiostatin level was greater compared with that in patients with well-developed collaterals (3.1 +/- 0.2 vs. 2.3 +/- 0.1 optical density units, P < 0.05). Neither MMP activities nor VEGF levels were different between the two groups of patients. The higher levels of angiostatin in patients with no visible collaterals were reflective of a higher concentration of plasmin/plasminogen (6.2 +/- 0.7 vs. 4.2 +/- 0.5 optical density units, P < 0.05) compared with those in patients with well-developed collateral vessels. Our results support the concept that the growth inhibitor angiostatin may have a negative impact on coronary collateral growth in patients. Perhaps therapies attempting to provoke coronary collateral growth should incorporate approaches to limit or neutralize the effects of growth inhibitors.
Authors:
Toshiro Matsunaga; William M Chilian; Keith March
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  288     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-20     Completed Date:  2005-05-31     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H2042-6     Citation Subset:  IM    
Affiliation:
Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan.
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MeSH Terms
Descriptor/Qualifier:
Aged
Angiostatins / metabolism*
Collateral Circulation / physiology*
Coronary Artery Bypass
Coronary Artery Disease / metabolism*,  physiopathology*,  surgery
Female
Fibrinolysin / metabolism
Humans
Male
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / metabolism
Middle Aged
Pericardial Effusion / metabolism
Plasminogen / metabolism
Vascular Endothelial Growth Factor A / metabolism
Grant Support
ID/Acronym/Agency:
HL-32788/HL/NHLBI NIH HHS; HL-65203/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Vascular Endothelial Growth Factor A; 86090-08-6/Angiostatins; 9001-91-6/Plasminogen; EC 3.4.21.7/Fibrinolysin; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9

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


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