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          Institute: MPI für molekulare Biomedizin     Collection: Jahrbuch 2018 (publ. 2017, arch)     Display Documents



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ID: 744123.0, MPI für molekulare Biomedizin / Jahrbuch 2018 (publ. 2017, arch)
Cx47 fine-tunes the handling of serum lipids but is dispensable for lymphatic vascular function
Authors:Meens, M. J.; Kutkut, I.; Rochemont, V.; Dubrot, J.; Kaladji, F. R.; Sabine, A.; Lyons, O.; Hendrikx, S.; Bernier-Latmani, J.; Kiefer, F.; Smith, A.; Hugues, S.; Petrova, T. V.; Kwak, B. R.
Date of Publication (YYYY-MM-DD):2017
Title of Journal:PLoS ONE
Volume:12
Issue / Number:7
Start Page:e0181476
Review Status:Internal review
Audience:Not Specified
Abstract / Description: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.
Free Keywords:Aging/metabolism/pathology; Animals; Apolipoproteins E/genetics/metabolism; Atherosclerosis/*metabolism/pathology; Cell Movement/physiology; Cholesterol, LDL/*blood; Collagen/metabolism; Connexins/genetics/*metabolism; Dendritic Cells/metabolism/pathology; Diet, High-Fat; Disease Models, Animal; Endothelial Cells/*metabolism/pathology; Fatty Acids/metabolism; Lymphatic Vessels/*metabolism/pathology; Macrophages/metabolism/pathology; Mice, Inbred C57BL; Mice, Knockout; T-Lymphocytes/metabolism/pathology; Triglycerides/*blood
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:MPI für molekulare Biomedizin
Affiliations:MPI für molekulare Biomedizin
External Affiliations:Department of Fundamental Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne, Switzerland. Division of Experimental Pathology, Institute of Pathology, CHUV, Lausanne, Switzerland. Academic Department of Vascular Surgery, Cardiovascular Division, King's College London, BHF Centre of Research Excellence & NIHR Biomedical Research Centre at King's Health Partners, St Thomas' Hospital, London, United Kingdom. Mammalian Cell Signalling Laboratory, Department of Vascular Cell Biology, Max Planck Institute for Molecular Biomedicine, Munster, Germany. Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland. Department of Medical Specialties - Cardiology, University of Geneva, Geneva, Switzerland.
Identifiers:ISSN:1932-6203 (Electronic) 1932-6203 (Linking) %R 10.1... [ID No:1]
URL:https://www.ncbi.nlm.nih.gov/pubmed/28732089 [ID No:2]
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