{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T10:15:23Z","timestamp":1780654523407,"version":"3.54.1"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Apoe\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              (apolipoprotein E deficient) mice were crossed with recessive yellow (Mc1r\n              <jats:sup>e\/e<\/jats:sup>\n              ) mice carrying dysfunctional MC1-R and fed a high-fat diet to induce atherosclerosis. Apoe\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              Mc1r\n              <jats:sup>e\/e<\/jats:sup>\n              mice developed significantly larger atherosclerotic lesions in the aortic sinus and in the whole aorta compared with Apoe\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              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\n              <jats:italic>Abca1<\/jats:italic>\n              and\n              <jats:italic>Abcg1<\/jats:italic>\n              expression in the aorta. Furthermore, Apoe\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              Mc1r\n              <jats:sup>e\/e<\/jats:sup>\n              mice showed a defect in bile acid metabolism that aggravated high-fat diet\u2013induced hypercholesterolemia and hepatic lipid accumulation. Flow cytometric analysis of leukocyte profile revealed that dysfunctional MC1-R enhanced arterial accumulation of classical Ly6C\n              <jats:sup>high<\/jats:sup>\n              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 Ly6C\n              <jats:sup>high<\/jats:sup>\n              monocytes, these cells had increased expression of L-selectin and P-selectin glycoprotein ligand 1.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.117.310418","type":"journal-article","created":{"date-parts":[[2017,12,28]],"date-time":"2017-12-28T10:00:49Z","timestamp":1514455249000},"page":"313-323","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["Melanocortin 1 Receptor Deficiency Promotes Atherosclerosis in Apolipoprotein E\n            <sup>\u2212\/\u2212<\/sup>\n            Mice"],"prefix":"10.1161","volume":"38","author":[{"given":"Petteri","family":"Rinne","sequence":"first","affiliation":[{"name":"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 Pharmacology, Turku University Hospital, Finland (E.S.); Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU), Munich, Germany (P.R., M.R., S.S.); and German Centre for..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Kadiri","sequence":"additional","affiliation":[{"name":"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 Pharmacology, Turku University Hospital, Finland (E.S.); Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU), Munich, Germany (P.R., M.R., S.S.); and German Centre for..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio","family":"Velasco-Delgado","sequence":"additional","affiliation":[{"name":"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 Pharmacology, Turku University Hospital, Finland (E.S.); Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU), Munich, Germany (P.R., M.R., S.S.); and German Centre for..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salla","family":"Nuutinen","sequence":"additional","affiliation":[{"name":"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 Pharmacology, Turku University Hospital, Finland (E.S.); Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU), Munich, Germany (P.R., M.R., S.S.); and German Centre for..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miro","family":"Viitala","sequence":"additional","affiliation":[{"name":"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 Pharmacology, Turku University Hospital, Finland (E.S.); Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU), Munich, Germany (P.R., M.R., S.S.); and German Centre for..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maija","family":"Hollm\u00e9n","sequence":"additional","affiliation":[{"name":"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 Pharmacology, Turku University Hospital, Finland (E.S.); Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU), Munich, Germany (P.R., M.R., S.S.); and German Centre for..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Rami","sequence":"additional","affiliation":[{"name":"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 Pharmacology, Turku University Hospital, Finland (E.S.); Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU), Munich, Germany (P.R., M.R., S.S.); and German Centre for..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eriika","family":"Savontaus","sequence":"additional","affiliation":[{"name":"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 Pharmacology, Turku University Hospital, Finland (E.S.); Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU), Munich, Germany (P.R., M.R., S.S.); and German Centre for..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Steffens","sequence":"additional","affiliation":[{"name":"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 Pharmacology, Turku University Hospital, Finland (E.S.); Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University (LMU), Munich, Germany (P.R., M.R., S.S.); and German Centre for..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1882"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3520"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0604260103"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29950"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00174-2"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.303565"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R800032-JLR200"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.113.302963"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.56.1.1"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1325670"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-1097.2011.00970.x"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.025889"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90572-8"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.300738"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2012.10.008"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33372"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.156935"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1175202"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11871"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28549"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.745091"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.771048"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3070"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.221127"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1189731"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.301086"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.59.2.248"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.158.7.3378"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.180521"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3258"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.12.001"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201201717"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2011.10.012"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.181.6.2259"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.149179"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.117.310418","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T22:45:22Z","timestamp":1715553922000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.117.310418"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2]]},"references-count":35,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1161\/ATVBAHA.117.310418"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.117.310418","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2]]},"assertion":[{"value":"2017-06-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}