Rapid Restoration of Normal Endothelial Functions in Genetically Hyperlipidemic Mice by a Synthetic Mediator of Reverse Lipid Transport
| Autor: | Allan M. Lefer, Wendi V. Rodrigueza, Kirstin D. Mazany, Kevin Jon Williams, Rosario Scalia |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Apolipoprotein E
medicine.medical_specialty Endothelium Vascular Cell Adhesion Molecule-1 Hyperlipidemias Biology Mice Apolipoproteins E In vivo Internal medicine Cell Adhesion Leukocytes medicine Animals Endothelial dysfunction Aorta Phospholipids Lipid Transport Mice Knockout Tumor Necrosis Factor-alpha Cell adhesion molecule Biological Transport Lipid metabolism Lipid Metabolism medicine.disease Vasodilation medicine.anatomical_structure Endocrinology Liver Liposomes Knockout mouse Female Endothelium Vascular Cardiology and Cardiovascular Medicine Interleukin-1 |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 20:1033-1039 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/01.atv.20.4.1033 |
| Popis: | Abstract —Endothelial dysfunction is a major pathophysiological consequence of hypercholesterolemia and other conditions. We examined whether a synthetic mediator of lipid transport from peripheral tissues to the liver (ie, the “reverse” pathway) could restore normal endothelial function in vivo. Using assays of macrovascular and microvascular function, we found that genetically hypercholesterolemic apolipoprotein E knockout mice exhibited key endothelial impairments. Treatment of the mice for 1 week with daily intravenous bolus injections of large “empty” phospholipid vesicles, which accelerate the reverse pathway in vivo, restored endothelium-dependent relaxation, leukocyte adherence, and endothelial expression of vascular cell adhesion molecule-1 to normal or nearly normal levels. These changes occurred despite the long-standing hyperlipidemia of the animals and the persistence of high serum concentrations of cholesterol-rich atherogenic lipoproteins during the treatment. Our results indicate that dysfunctional macrovascular and microvascular endothelium in apolipoprotein E knockout mice can recover relatively quickly in vivo and that accelerated reverse lipid transport may be a useful therapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|