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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Li, Chenghong Shyy, John Y-j Fu, Chenglai He, Jinlong Zhu, Yi |
| Description | Author Affiliation: Fu C ( Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Peking University Health Science Center, Beijing 100091, China.) |
| Abstract | Caveolae and its structural protein caveolin-1 (Cav-1) are abundant in vascular endothelial cells (ECs). We examined whether caveolae are involved in monocyte adhesion to ECs responding to a synergy of hypercholesterolemia and inflammation. Treating human umbilical vein ECs with cholesterol enhanced endotoxin lipopolysaccharide (LPS)-induced monocyte adhesion. Use of isolated caveolae-enriched membranes revealed that cell adhesion molecules (CAMs), including intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), co-localized with Cav-1 in caveolae. LPS upregulated CAMs expression and increased the co-localization. Cholesterol exposure decreased the level of CAMs in the caveolae. Co-immunoprecipitation and confocal microscopy revealed that ICAM-1 interacted with Cav-1. Electron microscopy showed that ICAM-1 was mainly located in caveolae. Cholesterol exposure decreased this interaction and drove ICAM-1 out of caveolae. Knockdown of Cav-1 reduced the synergistic effects of cholesterol and inflammation. In vivo, ICAM-1 and Cav-1 co-localization was lower in the aortic endothelium of $ApoE^{−/−}$ mice than in that of wild-type controls. Cav-1 negatively regulates monocyte adhesion by the co-localization of CAMs in caveolae, which is disturbed by cholesterol. Thus, our study suggests a molecular basis underlying the synergistic effects of hypercholesterolemia and inflammation in atherogenesis. |
| ISSN | 00063002 |
| Journal | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
| Issue Number | 7 |
| Volume Number | 1801 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2010-07-01 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | Caveolae Metabolism Cholesterol Endothelium, Vascular Hypercholesterolemia Monocytes Animals Apolipoproteins E Genetics Biological Transport Drug Effects Pathology Caveolin 1 Cell Adhesion Gene Expression Regulation Inflammation Intercellular Adhesion Molecule-1 Lipopolysaccharides Pharmacology Mice Mice, Knockout Vascular Cell Adhesion Molecule-1 Research Support, Non-U.S. Gov't Biochemistry |
| Content Type | Text |
| Resource Type | Article |
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