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Pannexin1 links lymphatic function to lipid metabolism and atherosclerosis

Roth, Christel
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Published in Scientific Reports. 2017, vol. 7, no. 1, p. 13706
Abstract 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.
PMID: 29057961
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Article (Published version) (10.1 MB) - public document Free access
Research groups L'athérosclérose (665)
Mucoviscidose et jonctions GAP (229)
Pathologie et immunologie (906)
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MOLICA, Filippo et al. Pannexin1 links lymphatic function to lipid metabolism and atherosclerosis. In: Scientific Reports, 2017, vol. 7, n° 1, p. 13706. doi: 10.1038/s41598-017-14130-4 https://archive-ouverte.unige.ch/unige:98457

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Deposited on : 2017-11-02

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