Document Detail

Endostatin binds biglycan and LDL and interferes with LDL retention to the subendothelial matrix during atherosclerosis.
MedLine Citation:
PMID:  15995169     Owner:  NLM     Status:  MEDLINE    
Retention of lipoproteins to proteoglycans in the subendothelial matrix (SEM) is an early event in atherosclerosis. We recently reported that collagen XVIII and its proteolytically released fragment endostatin (ES) are differentially depleted in blood vessels affected by atherosclerosis. Loss of collagen XVIII/ES in atherosclerosis-prone mice enhanced plaque neovascularization and increased the vascular permeability to lipids by distinct mechanisms. Impaired endothelial barrier function increased the influx of lipoproteins across the endothelium; however, we hypothesized that enhanced retention might be a second mechanism leading to the increased lipid content in atheromas lacking collagen XVIII. We now demonstrate a novel property of ES that binds both the matrix proteoglycan biglycan and LDL and interferes with LDL retention to biglycan and to SEM. A peptide encompassing the alpha coil in the ES crystal structure mediates the major blocking effect of ES on LDL retention. ES inhibits the macrophage uptake of biglycan-associated LDL indirectly by interfering with LDL retention to biglycan, but it has no direct effect on the macrophage uptake of native or modified lipoproteins. Thus, loss of ES in advanced atheromas enhances lipoprotein retention in SEM. Our data reveal a third protective role of this vascular basement membrane component during atherosclerosis.
Xiaokun Zeng; Joshua Chen; Yury I Miller; Kashi Javaherian; Karen S Moulton
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.     Date:  2005-07-01
Journal Detail:
Title:  Journal of lipid research     Volume:  46     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-08-16     Completed Date:  2005-10-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1849-59     Citation Subset:  IM    
Vascular Biology Program, Department of Surgery, Children's Hospital, Boston, MA 02115, USA.
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MeSH Terms
Aorta / chemistry
Arteriosclerosis / metabolism*
Basement Membrane / metabolism
Binding Sites
Binding, Competitive
Collagen Type XVIII / metabolism
Endostatins / analysis,  metabolism*,  pharmacology*
Endothelium / metabolism*
Extracellular Matrix Proteins
Glycosaminoglycans / metabolism
Lipoproteins / metabolism
Lipoproteins, LDL / metabolism*
Macrophages / metabolism
Macrophages, Peritoneal
Mice, Inbred C57BL
Proteoglycans / metabolism*
Recombinant Proteins
Umbilical Veins
Grant Support
Reg. No./Substance:
0/Collagen Type XVIII; 0/Endostatins; 0/Extracellular Matrix Proteins; 0/Glycosaminoglycans; 0/Lipoproteins; 0/Lipoproteins, LDL; 0/Proteoglycans; 0/Recombinant Proteins; 123939-84-4/biglycan

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