Phosphatidylethanol mediates its effects on the vascular endothelial growth factor via HDL receptor in endothelial cells
| Autor: | Markku J. Savolainen, Marja K. Liisanantti |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty Indoles medicine.medical_treatment CD36 Lipoproteins Blotting Western Carbazoles Medicine (miscellaneous) Enzyme-Linked Immunosorbent Assay Glycerophospholipids Toxicology Cell Line Maleimides chemistry.chemical_compound Internal medicine medicine Humans Scavenger receptor Enzyme Inhibitors Protein Kinase C Receptors Lipoprotein Flavonoids Mitogen-Activated Protein Kinase 1 biology Cholesterol Growth factor Reverse cholesterol transport Endothelial Cells Vascular endothelial growth factor Endothelial stem cell Psychiatry and Mental health Endocrinology chemistry Calcium-Calmodulin-Dependent Protein Kinases biology.protein lipids (amino acids peptides and proteins) Phosphatidylethanol Lipoproteins HDL |
| Zdroj: | Alcoholism, clinical and experimental research. 33(2) |
| ISSN: | 1530-0277 |
| Popis: | Background: Previous epidemiological studies have shown that light to moderate alcohol consumption has protective effects against coronary heart disease but the mechanisms of the beneficial effect of alcohol are not known. Ethanol may increase high density lipoprotein (HDL) cholesterol concentration, augment the reverse cholesterol transport, or regulate growth factors or adhesion molecules. To study whether qualitative changes in HDL phospholipids mediate part of the beneficial effects of alcohol on atherosclerosis by HDL receptor, we investigated whether phosphatidylethanol (PEth) in HDL particles affects the secretion of vascular endothelial growth factor (VEGF) by a human scavenger receptor CD36 and LIMPII analog-I (CLA-1)-mediated pathway. Methods: Human EA.hy 926 endothelial cells were incubated in the presence of native HDL or PEth-HDL. VEGF concentration and CLA-1 protein expression were measured. Human CLA-1 receptor-mediated mechanisms in endothelial cells were studied using CLA-1 blocking antibody and protein kinase inhibitors. Results: Phosphatidylethanol-containing HDL particles caused a 6-fold increase in the expression of CLA-1 in endothelial cells compared with the effect of native HDL. That emergent effect was mediated mainly through protein kinase C and p44/42 mitogen-activated protein kinase pathways. PEth increased the secretion of VEGF and that increase could be abolished by a CLA-1 blocking antibody. Conclusions: High density lipoprotein particles containing PEth bind to CLA-1 receptor and thereby increase the secretion of VEGF from endothelial cells. Ethanol-induced protective effects against coronary heart disease may be explained, at least partly, by the effects of PEth-modified HDL particles on VEGF via CLA-1-mediated mechanisms in endothelial cells. |
| Databáze: | OpenAIRE |
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