Cx47 fine-tunes the handling of serum lipids but is dispensable for lymphatic vascular function
Identifieur interne : 000650 ( Main/Exploration ); précédent : 000649; suivant : 000651Cx47 fine-tunes the handling of serum lipids but is dispensable for lymphatic vascular function
Auteurs : Merlijn J. Meens [Suisse] ; Issa Kutkut [Suisse] ; Viviane Rochemont [Suisse] ; Juan Dubrot [Suisse] ; Fouad R. Kaladji [Suisse] ; Amélie Sabine [Suisse] ; Oliver Lyons [Royaume-Uni] ; Stefanie Hendrikx [Suisse] ; Jeremiah Bernier-Latmani [Suisse] ; Friedemann Kiefer [Allemagne] ; Alberto Smith [Royaume-Uni] ; Stéphanie Hugues [Suisse] ; Tatiana V. Petrova [Suisse] ; Brenda R. Kwak [Suisse]Source :
- PLoS ONE [ 1932-6203 ] ; 2017.
Abstract
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
Url:
DOI: 10.1371/journal.pone.0181476
PubMed: 28732089
PubMed Central: 5521787
Affiliations:
- Allemagne, Royaume-Uni, Suisse
- Angleterre, Canton de Genève, Canton de Vaud, District de Münster, Grand Londres, Rhénanie-du-Nord-Westphalie
- Genève, Lausanne, Londres, Münster
- Université de Genève
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Petrova</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Fundamental Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Fundamental Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff003"><addr-line>Division of Experimental Pathology, Institute of Pathology, CHUV, Lausanne, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Division of Experimental Pathology, Institute of Pathology, CHUV, Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff006"><addr-line>Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology Lausanne, Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Kwak, Brenda R" sort="Kwak, Brenda R" uniqKey="Kwak B" first="Brenda R." last="Kwak">Brenda R. 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Meens</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Pathology and Immunology, University of Geneva, Geneva</wicri:regionArea><orgName type="university">Université de Genève</orgName><placeName><settlement type="city">Genève</settlement><region nuts="3" type="region">Canton de Genève</region></placeName></affiliation></author><author><name sortKey="Kutkut, Issa" sort="Kutkut, Issa" uniqKey="Kutkut I" first="Issa" last="Kutkut">Issa Kutkut</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Pathology and Immunology, University of Geneva, Geneva</wicri:regionArea><orgName type="university">Université de Genève</orgName><placeName><settlement type="city">Genève</settlement><region nuts="3" type="region">Canton de Genève</region></placeName></affiliation></author><author><name sortKey="Rochemont, Viviane" sort="Rochemont, Viviane" uniqKey="Rochemont V" first="Viviane" last="Rochemont">Viviane Rochemont</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Pathology and Immunology, University of Geneva, Geneva</wicri:regionArea><orgName type="university">Université de Genève</orgName><placeName><settlement type="city">Genève</settlement><region nuts="3" type="region">Canton de Genève</region></placeName></affiliation></author><author><name sortKey="Dubrot, Juan" sort="Dubrot, Juan" uniqKey="Dubrot J" first="Juan" last="Dubrot">Juan Dubrot</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Pathology and Immunology, University of Geneva, Geneva</wicri:regionArea><orgName type="university">Université de Genève</orgName><placeName><settlement type="city">Genève</settlement><region nuts="3" type="region">Canton de Genève</region></placeName></affiliation></author><author><name sortKey="Kaladji, Fouad R" sort="Kaladji, Fouad R" uniqKey="Kaladji F" first="Fouad R." last="Kaladji">Fouad R. Kaladji</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Pathology and Immunology, University of Geneva, Geneva</wicri:regionArea><orgName type="university">Université de Genève</orgName><placeName><settlement type="city">Genève</settlement><region nuts="3" type="region">Canton de Genève</region></placeName></affiliation></author><author><name sortKey="Sabine, Amelie" sort="Sabine, Amelie" uniqKey="Sabine A" first="Amélie" last="Sabine">Amélie Sabine</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Fundamental Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Fundamental Oncology, Centre Hospitalier Universitaire Vaudois 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Centre at King's Health Partners, St Thomas' Hospital, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>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</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Hendrikx, Stefanie" sort="Hendrikx, Stefanie" uniqKey="Hendrikx S" first="Stefanie" last="Hendrikx">Stefanie Hendrikx</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Fundamental Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Fundamental Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff003"><addr-line>Division of Experimental Pathology, Institute of Pathology, CHUV, Lausanne, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Division of Experimental Pathology, Institute of Pathology, CHUV, Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Bernier Latmani, Jeremiah" sort="Bernier Latmani, Jeremiah" uniqKey="Bernier Latmani J" first="Jeremiah" last="Bernier-Latmani">Jeremiah Bernier-Latmani</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Fundamental Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Fundamental Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff003"><addr-line>Division of Experimental Pathology, Institute of Pathology, CHUV, Lausanne, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Division of Experimental Pathology, Institute of Pathology, CHUV, Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Kiefer, Friedemann" sort="Kiefer, Friedemann" uniqKey="Kiefer F" first="Friedemann" last="Kiefer">Friedemann Kiefer</name><affiliation wicri:level="3"><nlm:aff id="aff005"><addr-line>Mammalian Cell Signalling Laboratory, Department of Vascular Cell Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Mammalian Cell Signalling Laboratory, Department of Vascular Cell Biology, Max Planck Institute for Molecular Biomedicine, Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author><author><name sortKey="Smith, Alberto" sort="Smith, Alberto" uniqKey="Smith A" first="Alberto" last="Smith">Alberto Smith</name><affiliation wicri:level="3"><nlm:aff id="aff004"><addr-line>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</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>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</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Hugues, Stephanie" sort="Hugues, Stephanie" uniqKey="Hugues S" first="Stéphanie" last="Hugues">Stéphanie Hugues</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Pathology and Immunology, University of Geneva, Geneva</wicri:regionArea><orgName type="university">Université de Genève</orgName><placeName><settlement type="city">Genève</settlement><region nuts="3" type="region">Canton de Genève</region></placeName></affiliation></author><author><name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V." last="Petrova">Tatiana V. Petrova</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Fundamental Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Fundamental Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff003"><addr-line>Division of Experimental Pathology, Institute of Pathology, CHUV, Lausanne, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Division of Experimental Pathology, Institute of Pathology, CHUV, Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff006"><addr-line>Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology Lausanne, Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Kwak, Brenda R" sort="Kwak, Brenda R" uniqKey="Kwak B" first="Brenda R." last="Kwak">Brenda R. Kwak</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Pathology and Immunology, University of Geneva, Geneva</wicri:regionArea><orgName type="university">Université de Genève</orgName><placeName><settlement type="city">Genève</settlement><region nuts="3" type="region">Canton de Genève</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff007"><addr-line>Department of Medical Specialties – Cardiology, University of Geneva, Geneva, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Medical Specialties – Cardiology, University of Geneva, Geneva</wicri:regionArea><orgName type="university">Université de Genève</orgName><placeName><settlement type="city">Genève</settlement><region nuts="3" type="region">Canton de Genève</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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 <italic>Cx47</italic><sup><italic>-/-</italic></sup> 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 (<italic>Apoe</italic><sup><italic>-/-</italic></sup>) mice, LDL-cholesterol was decreased in young <italic>Cx47</italic><sup><italic>-/-</italic></sup><italic>Apoe</italic><sup><italic>-/-</italic></sup> adults as compared to <italic>Apoe</italic><sup><italic>-/-</italic></sup> 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 <italic>Cx47</italic><sup><italic>-/-</italic></sup><italic>Apoe</italic><sup><italic>-/-</italic></sup> mice. These plaques contained fewer macrophages but similar amounts of T lymphocytes, collagen and lipids than plaques of <italic>Apoe</italic><sup><italic>-/-</italic></sup> mice. 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Zhang</name></author><author><name sortKey="Reddick, Rl" uniqKey="Reddick R">RL Reddick</name></author><author><name sortKey="Piedrahita, Ja" uniqKey="Piedrahita J">JA Piedrahita</name></author><author><name sortKey="Maeda, N" uniqKey="Maeda N">N Maeda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hagerling, R" uniqKey="Hagerling R">R Hagerling</name></author><author><name sortKey="Pollmann, C" uniqKey="Pollmann C">C Pollmann</name></author><author><name sortKey="Kremer, L" uniqKey="Kremer L">L Kremer</name></author><author><name sortKey="Andresen, V" uniqKey="Andresen V">V Andresen</name></author><author><name sortKey="Kiefer, F" uniqKey="Kiefer F">F Kiefer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Meens, Mj" uniqKey="Meens M">MJ Meens</name></author><author><name sortKey="Alonso, F" uniqKey="Alonso F">F Alonso</name></author><author><name sortKey="Le Gal, L" uniqKey="Le Gal L">L Le Gal</name></author><author><name sortKey="Kwak, Br" uniqKey="Kwak B">BR Kwak</name></author><author><name sortKey="Haefliger, Ja" uniqKey="Haefliger J">JA Haefliger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kwak, Br" uniqKey="Kwak B">BR Kwak</name></author><author><name sortKey="Veillard, N" uniqKey="Veillard N">N Veillard</name></author><author><name sortKey="Pelli, G" uniqKey="Pelli G">G Pelli</name></author><author><name sortKey="Mulhaupt, F" uniqKey="Mulhaupt F">F Mulhaupt</name></author><author><name sortKey="James, Rw" uniqKey="James R">RW James</name></author><author><name sortKey="Chanson, M" uniqKey="Chanson M">M Chanson</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li><li>Royaume-Uni</li><li>Suisse</li></country><region><li>Angleterre</li><li>Canton de Genève</li><li>Canton de Vaud</li><li>District de Münster</li><li>Grand Londres</li><li>Rhénanie-du-Nord-Westphalie</li></region><settlement><li>Genève</li><li>Lausanne</li><li>Londres</li><li>Münster</li></settlement><orgName><li>Université de Genève</li></orgName></list><tree><country name="Suisse"><region name="Canton de Genève"><name sortKey="Meens, Merlijn J" sort="Meens, Merlijn J" uniqKey="Meens M" first="Merlijn J." last="Meens">Merlijn J. Meens</name></region><name sortKey="Bernier Latmani, Jeremiah" sort="Bernier Latmani, Jeremiah" uniqKey="Bernier Latmani J" first="Jeremiah" last="Bernier-Latmani">Jeremiah Bernier-Latmani</name><name sortKey="Bernier Latmani, Jeremiah" sort="Bernier Latmani, Jeremiah" uniqKey="Bernier Latmani J" first="Jeremiah" last="Bernier-Latmani">Jeremiah Bernier-Latmani</name><name sortKey="Dubrot, Juan" sort="Dubrot, Juan" uniqKey="Dubrot J" first="Juan" last="Dubrot">Juan Dubrot</name><name sortKey="Hendrikx, Stefanie" sort="Hendrikx, Stefanie" uniqKey="Hendrikx S" first="Stefanie" last="Hendrikx">Stefanie Hendrikx</name><name sortKey="Hendrikx, Stefanie" sort="Hendrikx, Stefanie" uniqKey="Hendrikx S" first="Stefanie" last="Hendrikx">Stefanie Hendrikx</name><name sortKey="Hugues, Stephanie" sort="Hugues, Stephanie" uniqKey="Hugues S" first="Stéphanie" last="Hugues">Stéphanie Hugues</name><name sortKey="Kaladji, Fouad R" sort="Kaladji, Fouad R" uniqKey="Kaladji F" first="Fouad R." last="Kaladji">Fouad R. Kaladji</name><name sortKey="Kutkut, Issa" sort="Kutkut, Issa" uniqKey="Kutkut I" first="Issa" last="Kutkut">Issa Kutkut</name><name sortKey="Kwak, Brenda R" sort="Kwak, Brenda R" uniqKey="Kwak B" first="Brenda R." last="Kwak">Brenda R. Kwak</name><name sortKey="Kwak, Brenda R" sort="Kwak, Brenda R" uniqKey="Kwak B" first="Brenda R." last="Kwak">Brenda R. Kwak</name><name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V." last="Petrova">Tatiana V. Petrova</name><name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V." last="Petrova">Tatiana V. Petrova</name><name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V." last="Petrova">Tatiana V. Petrova</name><name sortKey="Rochemont, Viviane" sort="Rochemont, Viviane" uniqKey="Rochemont V" first="Viviane" last="Rochemont">Viviane Rochemont</name><name sortKey="Sabine, Amelie" sort="Sabine, Amelie" uniqKey="Sabine A" first="Amélie" last="Sabine">Amélie Sabine</name><name sortKey="Sabine, Amelie" sort="Sabine, Amelie" uniqKey="Sabine A" first="Amélie" last="Sabine">Amélie Sabine</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Lyons, Oliver" sort="Lyons, Oliver" uniqKey="Lyons O" first="Oliver" last="Lyons">Oliver Lyons</name></region><name sortKey="Smith, Alberto" sort="Smith, Alberto" uniqKey="Smith A" first="Alberto" last="Smith">Alberto Smith</name></country><country name="Allemagne"><region name="Rhénanie-du-Nord-Westphalie"><name sortKey="Kiefer, Friedemann" sort="Kiefer, Friedemann" uniqKey="Kiefer F" first="Friedemann" last="Kiefer">Friedemann Kiefer</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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