Pannexin1 links lymphatic function to lipid metabolism and atherosclerosis
| Autor: | Avigail Ehrlich, Brenda R. Kwak, Stéphanie Hugues, Laurent Vinet, Vincent Braunersreuther, Merlijn J. Meens, Graziano Pelli, Osman Ratib, Eliana Scemes, Marc Chanson, Juan Dubrot, Filippo Molica, Christel L Roth, Sandrine Morel |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Male medicine.medical_specialty lcsh:Medicine Nerve Tissue Proteins ddc:616.07 Diet High-Fat ddc:616.0757 Connexins Monocytes Article Apolipoproteins E Pathogenesis Lesion 03 medical and health sciences Internal medicine medicine Lymphatic vessel Extracellular Animals lcsh:Science Lymphatic Vessels Mice Knockout ddc:615 Multidisciplinary ddc:618 Chemistry Body Weight lcsh:R Endothelial Cells Lipid metabolism Extracellular Fluid Atherosclerosis Lipid Metabolism Dietary Fats ddc:616.8 Disease Models Animal 030104 developmental biology Endocrinology Lymphatic system medicine.anatomical_structure Carotid Arteries lcsh:Q medicine.symptom |
| Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) Scientific Reports Scientific Reports, Vol. 7, No 1 (2017) P. 13706 |
| ISSN: | 2045-2322 |
| Popis: | Extracellular ATP is a central signaling molecule in inflammatory responses. Pannexin1 (Panx1) channels release ATP in a controlled manner and have been implicated in various inflammatory pathologies, but their role in atherogenesis remains elusive. Using atherosclerosis-susceptible mouse models with ubiquitous deletion of Panx1 (Panx1 −/− Apoe −/− ) or with Cre recombinase-mediated deletion of Panx1 in endothelial cells and monocytes (Tie2-Cre Tg Panx1 fl/fl Apoe −/− ; Panx1 del Apoe −/− ), we identified a novel role for Panx1 in the lymphatic vasculature. Atherosclerotic lesion development in response to high-cholesterol diet was enhanced in Panx1 del Apoe −/− mice, pointing to an atheroprotective role for Panx1 in endothelial and/or monocytic cells. Unexpectedly, atherogenesis was not changed in mice with ubiquitous Panx1 deletion, but Panx1 −/− Apoe −/− mice displayed reduced body weight, serum cholesterol, triglycerides and free fatty acids, suggesting altered lipid metabolism in these Panx1-deficient mice. Mechanistically, Panx1 −/− Apoe −/− mice showed impairment of lymphatic vessel function with decreased drainage of interstitial fluids and reduced dietary fat absorption. Thus, the detrimental effect of Panx1 deletion in endothelial and/or monocytic cells during atherogenesis is counterbalanced by an opposite effect resulting from impaired lymphatic function in ubiquitous Panx1-deficient mice. Collectively, our findings unveil a pivotal role of Panx1 in linking lymphatic function to lipid metabolism and atherosclerotic plaque development. |
| Databáze: | OpenAIRE |
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