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Melanocortin 1 Receptor Deficiency Promotes Atherosclerosis in Apolipoprotein E-/- Mice.
Rinne, Petteri; Kadiri, James J; Velasco-Delgado, Mauricio; Nuutinen, Salla; Viitala, Miro; Hollmén, Maija; Rami, Martina; Savontaus, Eriika; Steffens, Sabine.
Afiliación
  • Rinne P; From the Institute of Biomedicine, Research Center for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, University of Turku, Finland (P.R., J.J.K., M.V.-D., S.N., E.S.); Medicity Research Laboratory Turku, University of Turku, Finland (M.V., M.H.); Unit of Clinical Pharmac
  • Kadiri JJ; From the Institute of Biomedicine, Research Center for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, University of Turku, Finland (P.R., J.J.K., M.V.-D., S.N., E.S.); Medicity Research Laboratory Turku, University of Turku, Finland (M.V., M.H.); Unit of Clinical Pharmac
  • Velasco-Delgado M; From the Institute of Biomedicine, Research Center for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, University of Turku, Finland (P.R., J.J.K., M.V.-D., S.N., E.S.); Medicity Research Laboratory Turku, University of Turku, Finland (M.V., M.H.); Unit of Clinical Pharmac
  • Nuutinen S; From the Institute of Biomedicine, Research Center for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, University of Turku, Finland (P.R., J.J.K., M.V.-D., S.N., E.S.); Medicity Research Laboratory Turku, University of Turku, Finland (M.V., M.H.); Unit of Clinical Pharmac
  • Viitala M; From the Institute of Biomedicine, Research Center for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, University of Turku, Finland (P.R., J.J.K., M.V.-D., S.N., E.S.); Medicity Research Laboratory Turku, University of Turku, Finland (M.V., M.H.); Unit of Clinical Pharmac
  • Hollmén M; From the Institute of Biomedicine, Research Center for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, University of Turku, Finland (P.R., J.J.K., M.V.-D., S.N., E.S.); Medicity Research Laboratory Turku, University of Turku, Finland (M.V., M.H.); Unit of Clinical Pharmac
  • Rami M; From the Institute of Biomedicine, Research Center for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, University of Turku, Finland (P.R., J.J.K., M.V.-D., S.N., E.S.); Medicity Research Laboratory Turku, University of Turku, Finland (M.V., M.H.); Unit of Clinical Pharmac
  • Savontaus E; From the Institute of Biomedicine, Research Center for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, University of Turku, Finland (P.R., J.J.K., M.V.-D., S.N., E.S.); Medicity Research Laboratory Turku, University of Turku, Finland (M.V., M.H.); Unit of Clinical Pharmac
  • Steffens S; From the Institute of Biomedicine, Research Center for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, University of Turku, Finland (P.R., J.J.K., M.V.-D., S.N., E.S.); Medicity Research Laboratory Turku, University of Turku, Finland (M.V., M.H.); Unit of Clinical Pharmac
Arterioscler Thromb Vasc Biol ; 38(2): 313-323, 2018 02.
Article en En | MEDLINE | ID: mdl-29284608
OBJECTIVE: The MC1-R (melanocortin 1 receptor) is expressed by monocytes and macrophages where it mediates anti-inflammatory actions. MC1-R also protects against macrophage foam cell formation primarily by promoting cholesterol efflux through the ABCA1 (ATP-binding cassette transporter subfamily A member 1) and ABCG1 (ATP-binding cassette transporter subfamily G member 1). In this study, we aimed to investigate whether global deficiency in MC1-R signaling affects the development of atherosclerosis. APPROACH AND RESULTS: Apoe-/- (apolipoprotein E deficient) mice were crossed with recessive yellow (Mc1re/e) mice carrying dysfunctional MC1-R and fed a high-fat diet to induce atherosclerosis. Apoe-/- Mc1re/e mice developed significantly larger atherosclerotic lesions in the aortic sinus and in the whole aorta compared with Apoe-/- controls. In terms of plaque composition, MC1-R deficiency was associated with less collagen and smooth muscle cells and increased necrotic core, indicative of more vulnerable lesions. These changes were accompanied by reduced Abca1 and Abcg1 expression in the aorta. Furthermore, Apoe-/- Mc1re/e mice showed a defect in bile acid metabolism that aggravated high-fat diet-induced hypercholesterolemia and hepatic lipid accumulation. Flow cytometric analysis of leukocyte profile revealed that dysfunctional MC1-R enhanced arterial accumulation of classical Ly6Chigh monocytes and macrophages, effects that were evident in mice fed a normal chow diet but not under high-fat diet conditions. In support of enhanced arterial recruitment of Ly6Chigh monocytes, these cells had increased expression of L-selectin and P-selectin glycoprotein ligand 1. CONCLUSIONS: The present study highlights the importance of MC1-R in the development of atherosclerosis. Deficiency in MC1-R signaling exacerbates atherosclerosis by disturbing cholesterol handling and by increasing arterial monocyte accumulation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aorta / Enfermedades de la Aorta / Monocitos / Receptor de Melanocortina Tipo 1 / Aterosclerosis / Placa Aterosclerótica / Ratones Noqueados para ApoE Límite: Animals Idioma: En Revista: Arterioscler Thromb Vasc Biol Asunto de la revista: ANGIOLOGIA Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aorta / Enfermedades de la Aorta / Monocitos / Receptor de Melanocortina Tipo 1 / Aterosclerosis / Placa Aterosclerótica / Ratones Noqueados para ApoE Límite: Animals Idioma: En Revista: Arterioscler Thromb Vasc Biol Asunto de la revista: ANGIOLOGIA Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos