UNIGE document Scientific Article
previous document  unige:98457  next document
add to browser collection
Title

Pannexin1 links lymphatic function to lipid metabolism and atherosclerosis

Authors
Roth, Christel
show hidden authors show all authors [1 - 14]
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.
Identifiers
PMID: 29057961
Full text
Article (Published version) (10.1 MB) - public document Free access
Structures
Research groups L'athérosclérose (665)
Mucoviscidose et jonctions GAP (229)
Pathologie et immunologie (906)
Citation
(ISO format)
MOLICA, Filippo et al. Pannexin1 links lymphatic function to lipid metabolism and atherosclerosis. In: Scientific Reports, 2017, vol. 7, n° 1, p. 13706. https://archive-ouverte.unige.ch/unige:98457

103 hits

13 downloads

Update

Deposited on : 2017-11-02

Export document
Format :
Citation style :