Endostatin binds biglycan and LDL and interferes with LDL retention to the subendothelial matrix during atherosclerosis
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 col...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2005-09-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S002222752032931X |
| _version_ | 1818640075006672896 |
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| author | Xiaokun Zeng Joshua Chen Yury I. Miller Kashi Javaherian Karen S. Moulton |
| author_facet | Xiaokun Zeng Joshua Chen Yury I. Miller Kashi Javaherian Karen S. Moulton |
| author_sort | Xiaokun Zeng |
| collection | DOAJ |
| description | 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 α 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. |
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| format | Article |
| id | doaj.art-d80d50c2ebbd4aafa96e628fb0bca127 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-16T23:05:30Z |
| publishDate | 2005-09-01 |
| publisher | Elsevier |
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| series | Journal of Lipid Research |
| spelling | doaj.art-d80d50c2ebbd4aafa96e628fb0bca1272022-12-21T22:12:35ZengElsevierJournal of Lipid Research0022-22752005-09-0146918491859Endostatin binds biglycan and LDL and interferes with LDL retention to the subendothelial matrix during atherosclerosisXiaokun Zeng0Joshua Chen1Yury I. Miller2Kashi Javaherian3Karen S. Moulton4Vascular Biology Program, Department of Surgery, Children's Hospital, Boston, MA 02115Vascular Biology Program, Department of Surgery, Children's Hospital, Boston, MA 02115Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA 92093Vascular Biology Program, Department of Surgery, Children's Hospital, Boston, MA 02115To whom correspondence should be addressed.; Vascular Biology Program, Department of Surgery, Children's Hospital, Boston, MA 02115; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115Retention 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 α 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.http://www.sciencedirect.com/science/article/pii/S002222752032931Xlow density lipoproteinextracellular matrixvascular basement membraneproteoglycanscollagen XVIII |
| spellingShingle | Xiaokun Zeng Joshua Chen Yury I. Miller Kashi Javaherian Karen S. Moulton Endostatin binds biglycan and LDL and interferes with LDL retention to the subendothelial matrix during atherosclerosis Journal of Lipid Research low density lipoprotein extracellular matrix vascular basement membrane proteoglycans collagen XVIII |
| title | Endostatin binds biglycan and LDL and interferes with LDL retention to the subendothelial matrix during atherosclerosis |
| title_full | Endostatin binds biglycan and LDL and interferes with LDL retention to the subendothelial matrix during atherosclerosis |
| title_fullStr | Endostatin binds biglycan and LDL and interferes with LDL retention to the subendothelial matrix during atherosclerosis |
| title_full_unstemmed | Endostatin binds biglycan and LDL and interferes with LDL retention to the subendothelial matrix during atherosclerosis |
| title_short | Endostatin binds biglycan and LDL and interferes with LDL retention to the subendothelial matrix during atherosclerosis |
| title_sort | endostatin binds biglycan and ldl and interferes with ldl retention to the subendothelial matrix during atherosclerosis |
| topic | low density lipoprotein extracellular matrix vascular basement membrane proteoglycans collagen XVIII |
| url | http://www.sciencedirect.com/science/article/pii/S002222752032931X |
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