Cx47 fine-tunes the handling of serum lipids but is dispensable for lymphatic vascular function

Article Article scientifique Article Cx47 fine-tunes the handling of serum lipids but is dispensable for lymphatic vascular function eng 2017 author Meens Merlijn 767675 author Kutkut Issa Hussein Yousof 810493 author Rochemont Viviane author Dubrot Armendariz Juan 744966 author Kaladji Fouad Rami 771249 author Sabine Amélie author Lyons Oliver author Hendrikx Stefanie author Bernier-Latmani Jeremiah author Kiefer Friedemann author Smith Alberto author Hugues Stéphanie 663452 author Petrova Tatiana V author Kwak Brenda 0000-0003-0015-0044 113350 e0181476 10.1371/journal.pone.0181476 28732089 1932-6203 Mutations in the gap junction protein connexin47 (Cx47) are associated with lymphedema. However, the role of Cx47 in lymphatic pathophysiology is unknown. We demonstrate that Cx47 is expressed in lymphatic endothelial cells by whole-mount immunostaining and qPCR. To determine if Cx47 plays a role in lymphatic vessel function we analysed Cx47-/- mice. Cx47-deficiency did not affect lymphatic contractility (contractile amplitude or frequency) or lymphatic morphology (vessel diameter or number of valves). Interstitial fluid drainage or dendritic cell migration through lymphatic vessels was also not affected by Cx47-deficiency. Cx47 is dispensable for long-chain fatty acid absorption from the gut but rather promotes serum lipid handling as prolonged elevated triglyceride levels were observed in Cx47-deficient mice after oral lipid tolerance tests. When crossed with Apolipoprotein E-deficient (Apoe-/-) mice, LDL-cholesterol was decreased in young Cx47-/-Apoe-/- adults as compared to Apoe-/- mice, which was inverted later in life. Finally, advanced atherosclerotic plaques in thoracic-abdominal aortas of 15 months-old mice tended to be larger in Cx47-/-Apoe-/- mice. These plaques contained fewer macrophages but similar amounts of T lymphocytes, collagen and lipids than plaques of Apoe-/- mice. In conclusion, Cx47 is expressed in lymphatic endothelium and seems modestly implicated in multiple aspects of lymphatic pathophysiology. Dewey 616 Dewey 616.07 137 Département de pathologie et immunologie 21F 56 Département de médecine 221 false 397 Connexines et pathologies cardiovasculaires 665 563 Pathologie et immunologie 906 PLOS ONE 12 7 2404f51a-58a1-403d-a07b-e47c6b710522 Article (Published version) Public 28732089.pdf 3513190 application/pdf CC BY openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département de médecine

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Cx47 fine-tunes the handling of serum lipids but is dispensable for lymphatic vascular function	PLOS ONE			2017	532	337

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Kaladji, Fouad Rami