LYMPHATIC VESSEL INSUFFICIENCY IN HYPERCHOLESTEROLEMIC MICE ALTERS LIPOPROTEIN LEVELS AND PROMOTES ATHEROGENESIS
Identifieur interne : 002954 ( Main/Exploration ); précédent : 002953; suivant : 002955LYMPHATIC VESSEL INSUFFICIENCY IN HYPERCHOLESTEROLEMIC MICE ALTERS LIPOPROTEIN LEVELS AND PROMOTES ATHEROGENESIS
Auteurs : Taina Vuorio [Finlande] ; Harri Nurmi [Finlande] ; Karen Moulton [États-Unis] ; Jere Pikkarainen [Finlande] ; Marius R. Robciuc [Finlande] ; Miina Öhman [Finlande] ; Suvi E. Heinonen [Finlande] ; Haritha Samaranayake [Finlande] ; Tommi Heikura [Finlande] ; Kari Alitalo [Finlande] ; Seppo Yl Herttuala [Finlande]Source :
- Arteriosclerosis, thrombosis, and vascular biology [ 1079-5642 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Apolipoprotéines B (physiologie), Athérosclérose (étiologie), Cholestérol (métabolisme), Humains, Hypercholestérolémie (), Lipides (sang), Lipoprotéines (métabolisme), Récepteur-3 au facteur croissance endothéliale vasculaire (physiologie), Récepteurs aux lipoprotéines LDL (physiologie), Souris, Souris de lignée C57BL, Souris transgéniques, Vaisseaux lymphatiques (physiopathologie).
- MESH :
- métabolisme : Cholestérol, Lipoprotéines.
- physiologie : Apolipoprotéines B, Récepteur-3 au facteur croissance endothéliale vasculaire, Récepteurs aux lipoprotéines LDL.
- physiopathologie : Vaisseaux lymphatiques.
- sang : Lipides.
- étiologie : Athérosclérose.
- Animaux, Humains, Hypercholestérolémie, Souris, Souris de lignée C57BL, Souris transgéniques.
English descriptors
- KwdEn :
- Animals, Apolipoproteins B (physiology), Atherosclerosis (etiology), Cholesterol (metabolism), Humans, Hypercholesterolemia (complications), Lipids (blood), Lipoproteins (metabolism), Lymphatic Vessels (physiopathology), Mice, Mice, Inbred C57BL, Mice, Transgenic, Receptors, LDL (physiology), Vascular Endothelial Growth Factor Receptor-3 (physiology).
- MESH :
- chemical , blood : Lipids.
- chemical , metabolism : Cholesterol, Lipoproteins.
- chemical , physiology : Apolipoproteins B, Receptors, LDL, Vascular Endothelial Growth Factor Receptor-3.
- complications : Hypercholesterolemia.
- etiology : Atherosclerosis.
- physiopathology : Lymphatic Vessels.
- Animals, Humans, Mice, Mice, Inbred C57BL, Mice, Transgenic.
Abstract
Lymphatic vessels collect extravasated fluid and proteins from tissues to blood circulation as well as play an essential role in lipid metabolism by taking up intestinal chylomicrons. Previous studies have shown that impairment of lymphatic vessel function causes lymphedema and fat accumulation, but clear connections between arterial pathologies and lymphatic vessels have not been described.
Two transgenic mouse strains with lymphatic insufficiency (sVEGFR3 and Chy) were crossed with atherosclerotic mice (LDLR−/−/ApoB100/100) to study the effects of insufficient lymphatic vessel transport on lipoprotein metabolism and atherosclerosis. Both sVEGFR3 × LDLR−/−/ApoB100/100 mice and Chy × LDLR−/−/ApoB100/100 mice had higher plasma cholesterol levels compared to LDLR−/−/ApoB100/100 control mice during both normal chow diet (16.3 mmol/l and 13.7 mmol/l vs. 8.2 mmol/l, respectively) and Western-type high fat diet (e.g. after 2 weeks of fat diet 45.9 mmol/l and 42.6 mmol/l vs. 30.2 mmol/l, respectively). Cholesterol and triglyceride levels in very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) fractions were increased. Atherosclerotic lesions in young and intermediate cohorts of sVEGFR3 × LDLR−/−/ApoB100/100 mice progressed faster than in control mice (e.g. intermediate cohort mice at 6 weeks 18.3% vs. 7.7% of the whole aorta, respectively). In addition, lesions in sVEGFR3 × LDLR−/−/ApoB100/100 mice and Chy × LDLR−/−/ApoB100/100 mice had much less lymphatic vessels than lesions in control mice (0.33% and 1.07% vs. 7.45% of podoplanin positive vessels, respectively).
We show a novel finding linking impaired lymphatic vessels to lipoprotein metabolism, increased plasma cholesterol levels and enhanced atherogenesis.
Url:
DOI: 10.1161/ATVBAHA.114.302528
PubMed: 24723556
PubMed Central: 4031366
Affiliations:
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Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio</wicri:regionArea><wicri:noRegion>FI-70211 Kuopio</wicri:noRegion></affiliation></author><author><name sortKey="Robciuc, Marius R" sort="Robciuc, Marius R" uniqKey="Robciuc M" first="Marius R." last="Robciuc">Marius R. Robciuc</name><affiliation wicri:level="4"><nlm:aff id="A2">Wihuri Research Institute and Translational Biology Program, Biomedicum Helsinki, Haartmaninkatu 8 (P.O. 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Box 63), FI-00014 University of Helsinki, Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Wihuri Research Institute and Translational Biology Program, Biomedicum Helsinki, Haartmaninkatu 8 (P.O. Box 63), FI-00014 University of Helsinki, Helsinki</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Heinonen, Suvi E" sort="Heinonen, Suvi E" uniqKey="Heinonen S" first="Suvi E." last="Heinonen">Suvi E. Heinonen</name><affiliation wicri:level="1"><nlm:aff id="A1">A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio</wicri:regionArea><wicri:noRegion>FI-70211 Kuopio</wicri:noRegion></affiliation></author><author><name sortKey="Samaranayake, Haritha" sort="Samaranayake, Haritha" uniqKey="Samaranayake H" first="Haritha" last="Samaranayake">Haritha Samaranayake</name><affiliation wicri:level="1"><nlm:aff id="A1">A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio</wicri:regionArea><wicri:noRegion>FI-70211 Kuopio</wicri:noRegion></affiliation></author><author><name sortKey="Heikura, Tommi" sort="Heikura, Tommi" uniqKey="Heikura T" first="Tommi" last="Heikura">Tommi Heikura</name><affiliation wicri:level="1"><nlm:aff id="A1">A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio</wicri:regionArea><wicri:noRegion>FI-70211 Kuopio</wicri:noRegion></affiliation></author><author><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><affiliation wicri:level="4"><nlm:aff id="A2">Wihuri Research Institute and Translational Biology Program, Biomedicum Helsinki, Haartmaninkatu 8 (P.O. Box 63), FI-00014 University of Helsinki, Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Wihuri Research Institute and Translational Biology Program, Biomedicum Helsinki, Haartmaninkatu 8 (P.O. 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Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio</wicri:regionArea><wicri:noRegion>FI-70211 Kuopio</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A4">Gene Therapy Unit, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Gene Therapy Unit, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio</wicri:regionArea><wicri:noRegion>FI-70211 Kuopio</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A5">Research Unit, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Research Unit, Kuopio University Hospital, P.O. 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Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio</wicri:regionArea><wicri:noRegion>FI-70211 Kuopio</wicri:noRegion></affiliation></author><author><name sortKey="Nurmi, Harri" sort="Nurmi, Harri" uniqKey="Nurmi H" first="Harri" last="Nurmi">Harri Nurmi</name><affiliation wicri:level="4"><nlm:aff id="A2">Wihuri Research Institute and Translational Biology Program, Biomedicum Helsinki, Haartmaninkatu 8 (P.O. Box 63), FI-00014 University of Helsinki, Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Wihuri Research Institute and Translational Biology Program, Biomedicum Helsinki, Haartmaninkatu 8 (P.O. Box 63), FI-00014 University of Helsinki, Helsinki</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Moulton, Karen" sort="Moulton, Karen" uniqKey="Moulton K" first="Karen" last="Moulton">Karen Moulton</name><affiliation wicri:level="1"><nlm:aff id="A3">Cardiology Division, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cardiology Division, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045</wicri:regionArea><wicri:noRegion>CO 80045</wicri:noRegion></affiliation></author><author><name sortKey="Pikkarainen, Jere" sort="Pikkarainen, Jere" uniqKey="Pikkarainen J" first="Jere" last="Pikkarainen">Jere Pikkarainen</name><affiliation wicri:level="1"><nlm:aff id="A1">A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio</wicri:regionArea><wicri:noRegion>FI-70211 Kuopio</wicri:noRegion></affiliation></author><author><name sortKey="Robciuc, Marius R" sort="Robciuc, Marius R" uniqKey="Robciuc M" first="Marius R." last="Robciuc">Marius R. Robciuc</name><affiliation wicri:level="4"><nlm:aff id="A2">Wihuri Research Institute and Translational Biology Program, Biomedicum Helsinki, Haartmaninkatu 8 (P.O. Box 63), FI-00014 University of Helsinki, Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Wihuri Research Institute and Translational Biology Program, Biomedicum Helsinki, Haartmaninkatu 8 (P.O. Box 63), FI-00014 University of Helsinki, Helsinki</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Ohman, Miina" sort="Ohman, Miina" uniqKey="Ohman M" first="Miina" last="Öhman">Miina Öhman</name><affiliation wicri:level="4"><nlm:aff id="A2">Wihuri Research Institute and Translational Biology Program, Biomedicum Helsinki, Haartmaninkatu 8 (P.O. Box 63), FI-00014 University of Helsinki, Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Wihuri Research Institute and Translational Biology Program, Biomedicum Helsinki, Haartmaninkatu 8 (P.O. Box 63), FI-00014 University of Helsinki, Helsinki</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Heinonen, Suvi E" sort="Heinonen, Suvi E" uniqKey="Heinonen S" first="Suvi E." last="Heinonen">Suvi E. Heinonen</name><affiliation wicri:level="1"><nlm:aff id="A1">A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio</wicri:regionArea><wicri:noRegion>FI-70211 Kuopio</wicri:noRegion></affiliation></author><author><name sortKey="Samaranayake, Haritha" sort="Samaranayake, Haritha" uniqKey="Samaranayake H" first="Haritha" last="Samaranayake">Haritha Samaranayake</name><affiliation wicri:level="1"><nlm:aff id="A1">A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio</wicri:regionArea><wicri:noRegion>FI-70211 Kuopio</wicri:noRegion></affiliation></author><author><name sortKey="Heikura, Tommi" sort="Heikura, Tommi" uniqKey="Heikura T" first="Tommi" last="Heikura">Tommi Heikura</name><affiliation wicri:level="1"><nlm:aff id="A1">A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio</wicri:regionArea><wicri:noRegion>FI-70211 Kuopio</wicri:noRegion></affiliation></author><author><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><affiliation wicri:level="4"><nlm:aff id="A2">Wihuri Research Institute and Translational Biology Program, Biomedicum Helsinki, Haartmaninkatu 8 (P.O. Box 63), FI-00014 University of Helsinki, Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Wihuri Research Institute and Translational Biology Program, Biomedicum Helsinki, Haartmaninkatu 8 (P.O. Box 63), FI-00014 University of Helsinki, Helsinki</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><orgName type="university">Université d'Helsinki</orgName></affiliation></author><author><name sortKey="Yl Herttuala, Seppo" sort="Yl Herttuala, Seppo" uniqKey="Yl Herttuala S" first="Seppo" last="Yl Herttuala">Seppo Yl Herttuala</name><affiliation wicri:level="1"><nlm:aff id="A1">A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio</wicri:regionArea><wicri:noRegion>FI-70211 Kuopio</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A4">Gene Therapy Unit, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Gene Therapy Unit, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio</wicri:regionArea><wicri:noRegion>FI-70211 Kuopio</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A5">Research Unit, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Research Unit, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio</wicri:regionArea><wicri:noRegion>FI-70211 Kuopio</wicri:noRegion></affiliation></author></analytic><series><title level="j">Arteriosclerosis, thrombosis, and vascular biology</title><idno type="ISSN">1079-5642</idno><idno type="eISSN">1524-4636</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Apolipoproteins B (physiology)</term><term>Atherosclerosis (etiology)</term><term>Cholesterol (metabolism)</term><term>Humans</term><term>Hypercholesterolemia (complications)</term><term>Lipids (blood)</term><term>Lipoproteins (metabolism)</term><term>Lymphatic Vessels (physiopathology)</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Transgenic</term><term>Receptors, LDL (physiology)</term><term>Vascular Endothelial Growth Factor Receptor-3 (physiology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Apolipoprotéines B (physiologie)</term><term>Athérosclérose (étiologie)</term><term>Cholestérol (métabolisme)</term><term>Humains</term><term>Hypercholestérolémie ()</term><term>Lipides (sang)</term><term>Lipoprotéines (métabolisme)</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire (physiologie)</term><term>Récepteurs aux lipoprotéines LDL (physiologie)</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris transgéniques</term><term>Vaisseaux lymphatiques (physiopathologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Lipids</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cholesterol</term><term>Lipoproteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Apolipoproteins B</term><term>Receptors, LDL</term><term>Vascular Endothelial Growth Factor Receptor-3</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Hypercholesterolemia</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Atherosclerosis</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cholestérol</term><term>Lipoprotéines</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Apolipoprotéines B</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire</term><term>Récepteurs aux lipoprotéines LDL</term></keywords><keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr"><term>Vaisseaux lymphatiques</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Lymphatic Vessels</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Lipides</term></keywords><keywords scheme="MESH" qualifier="étiologie" xml:lang="fr"><term>Athérosclérose</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Humans</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Transgenic</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Humains</term><term>Hypercholestérolémie</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris transgéniques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Objective</title><p id="P1">Lymphatic vessels collect extravasated fluid and proteins from tissues to blood circulation as well as play an essential role in lipid metabolism by taking up intestinal chylomicrons. Previous studies have shown that impairment of lymphatic vessel function causes lymphedema and fat accumulation, but clear connections between arterial pathologies and lymphatic vessels have not been described.</p></sec><sec id="S2"><title>Approach and Results</title><p id="P2">Two transgenic mouse strains with lymphatic insufficiency (sVEGFR3 and Chy) were crossed with atherosclerotic mice (LDLR<sup>−/−</sup>/ApoB<sup>100/100</sup>) to study the effects of insufficient lymphatic vessel transport on lipoprotein metabolism and atherosclerosis. Both sVEGFR3 × LDLR<sup>−/−</sup>/ApoB<sup>100/100</sup> mice and Chy × LDLR<sup>−/−</sup>/ApoB<sup>100/100</sup> mice had higher plasma cholesterol levels compared to LDLR<sup>−/−</sup>/ApoB<sup>100/100</sup> control mice during both normal chow diet (16.3 mmol/l and 13.7 mmol/l vs. 8.2 mmol/l, respectively) and Western-type high fat diet (e.g. after 2 weeks of fat diet 45.9 mmol/l and 42.6 mmol/l vs. 30.2 mmol/l, respectively). Cholesterol and triglyceride levels in very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) fractions were increased. Atherosclerotic lesions in young and intermediate cohorts of sVEGFR3 × LDLR<sup>−/−</sup>/ApoB<sup>100/100</sup> mice progressed faster than in control mice (e.g. intermediate cohort mice at 6 weeks 18.3% vs. 7.7% of the whole aorta, respectively). In addition, lesions in sVEGFR3 × LDLR<sup>−/−</sup>/ApoB<sup>100/100</sup> mice and Chy × LDLR<sup>−/−</sup>/ApoB<sup>100/100</sup> mice had much less lymphatic vessels than lesions in control mice (0.33% and 1.07% vs. 7.45% of podoplanin positive vessels, respectively).</p></sec><sec id="S3"><title>Conclusions</title><p id="P3">We show a novel finding linking impaired lymphatic vessels to lipoprotein metabolism, increased plasma cholesterol levels and enhanced atherogenesis.</p></sec></div></front></TEI><affiliations><list><country><li>Finlande</li><li>États-Unis</li></country><region><li>Uusimaa</li></region><settlement><li>Helsinki</li></settlement><orgName><li>Université d'Helsinki</li></orgName></list><tree><country name="Finlande"><noRegion><name sortKey="Vuorio, Taina" sort="Vuorio, Taina" uniqKey="Vuorio T" first="Taina" last="Vuorio">Taina Vuorio</name></noRegion><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><name sortKey="Heikura, Tommi" sort="Heikura, Tommi" uniqKey="Heikura T" first="Tommi" last="Heikura">Tommi Heikura</name><name sortKey="Heinonen, Suvi E" sort="Heinonen, Suvi E" uniqKey="Heinonen S" first="Suvi E." last="Heinonen">Suvi E. Heinonen</name><name sortKey="Nurmi, Harri" sort="Nurmi, Harri" uniqKey="Nurmi H" first="Harri" last="Nurmi">Harri Nurmi</name><name sortKey="Ohman, Miina" sort="Ohman, Miina" uniqKey="Ohman M" first="Miina" last="Öhman">Miina Öhman</name><name sortKey="Pikkarainen, Jere" sort="Pikkarainen, Jere" uniqKey="Pikkarainen J" first="Jere" last="Pikkarainen">Jere Pikkarainen</name><name sortKey="Robciuc, Marius R" sort="Robciuc, Marius R" uniqKey="Robciuc M" first="Marius R." last="Robciuc">Marius R. Robciuc</name><name sortKey="Samaranayake, Haritha" sort="Samaranayake, Haritha" uniqKey="Samaranayake H" first="Haritha" last="Samaranayake">Haritha Samaranayake</name><name sortKey="Yl Herttuala, Seppo" sort="Yl Herttuala, Seppo" uniqKey="Yl Herttuala S" first="Seppo" last="Yl Herttuala">Seppo Yl Herttuala</name><name sortKey="Yl Herttuala, Seppo" sort="Yl Herttuala, Seppo" uniqKey="Yl Herttuala S" first="Seppo" last="Yl Herttuala">Seppo Yl Herttuala</name><name sortKey="Yl Herttuala, Seppo" sort="Yl Herttuala, Seppo" uniqKey="Yl Herttuala S" first="Seppo" last="Yl Herttuala">Seppo Yl Herttuala</name></country><country name="États-Unis"><noRegion><name sortKey="Moulton, Karen" sort="Moulton, Karen" uniqKey="Moulton K" first="Karen" last="Moulton">Karen Moulton</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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