Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice
| Autor: | Brian Fulp, Mary G. Sorci-Thomas, Daniel Kreisel, Alan R. Tall, Melody A. Swartz, Marit Westerterp, Gwendalyn J. Randolph, Shu Hsia Chen, Emmanuel L. Gautier, Catherine Martel, Michael J. Thomas, Andrew M. Platt, Wenjun Li, Robert Bittman |
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| Přispěvatelé: | Medical Biochemistry |
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Gene Expression Aorta Thoracic Mice Transgenic Vascular permeability 030204 cardiovascular system & hematology Biology Cholesterol analog Capillary Permeability Carcinoma Lewis Lung Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine.artery medicine Lymphatic vessel Animals Macrophage Skin Lymphatic Vessels 030304 developmental biology Mice Inbred C3H 0303 health sciences Aorta Cholesterol Macrophages Reverse cholesterol transport General Medicine Sinus of Valsalva Atherosclerosis Vascular Endothelial Growth Factor Receptor-3 3. Good health Mice Inbred C57BL Kinetics Endocrinology medicine.anatomical_structure Lymphatic system chemistry Immunology Commentary lipids (amino acids peptides and proteins) Research Article |
| Zdroj: | Journal of clinical investigation, 123(4), 1571-1579. The American Society for Clinical Investigation |
| ISSN: | 0021-9738 |
| Popis: | Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic drainage from skin - 1 surgical and the other genetic - to quantitatively track RCT following injection of [H-3]-cholesterol-loaded macrophages upstream of blocked or absent lymphatic vessels. Macrophage RCT was markedly impaired in both models, even at sites with a leaky vasculature. Inhibited RCT was downstream of cholesterol efflux from macrophages, since macrophage efflux of a fluorescent cholesterol analog (BODIPY-cholesterol) was not altered by impaired lymphatic drainage. We next addressed whether RCT was mediated by lymphatic vessels from the aortic wall by loading the aortae of donor atherosclerotic Apoe-deficient mice with [H-2](6)-labeled cholesterol and surgically transplanting these aortae into recipient Apoe-deficient mice that were treated with anti-VEGFR3 antibody to block lymphatic regrowth or with control antibody to allow such regrowth. [H-2]-Cholesterol was retained in aortae of anti-VEGFR3-treated mice. Thus, the lymphatic vessel route is critical for RCT from multiple tissues, including the aortic wall. These results suggest that supporting lymphatic transport function may facilitate cholesterol clearance in therapies aimed at reversing atherosclerosis. |
| Databáze: | OpenAIRE |
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