{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:04:36Z","timestamp":1792087476952,"version":"4.4.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>\n                      Antibody blockade of the \u201cdo not eat me\u201d signal CD47 (cluster of differentiation 47) enhances efferocytosis and reduces lesion size and necrotic core formation in murine atherosclerosis. TNF (Tumor necrosis factor)-\u03b1 expression directly enhances\n                      <jats:italic>CD47<\/jats:italic>\n                      expression, and elevated TNF-\u03b1 is observed in the absence of the proefferocytosis receptor LRP1 (low-density lipoprotein receptor-related protein 1), a regulator of atherogenesis and inflammation. Thus, we tested the hypothesis that CD47 blockade requires the presence of macrophage LRP1 to enhance efferocytosis, temper TNF-\u03b1-dependent inflammation, and limit atherosclerosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results:<\/jats:title>\n                    <jats:p>\n                      Mice lacking systemic apoE (apoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ), alone or in combination with the loss of macrophage LRP1 (double knockout), were fed a Western-type diet for 12 weeks while receiving anti-CD47 antibody (anti-CD47) or IgG every other day. In apoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice, treatment with anti-CD47 reduced lesion size by 25.4%, decreased necrotic core area by 34.5%, and decreased the ratio of free:macrophage-associated apoptotic bodies by 47.6% compared with IgG controls (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.05), confirming previous reports. Double knockout mice treated with anti-CD47 showed no differences in lesion size, necrotic core area, or the ratio of free:macrophage-associated apoptotic bodies compared with IgG controls. In vitro efferocytosis was 30% higher when apoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      phagocytes were incubated with anti-CD47 compared with IgG controls (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.05); however, anti-CD47 had no effect on efferocytosis in double knockout phagocytes. Analyses of mRNA and protein showed increased CD47 expression in anti-inflammatory IL (interleukin)-4 treated LRP1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      macrophages compared with wild type, but no differences were observed in inflammatory lipopolysaccharide-treated macrophages.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      The proefferocytosis receptor LRP1 in macrophages is necessary for anti-CD47 blockade to enhance efferocytosis, limit atherogenesis, and decrease necrotic core formation in the apoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      model of atherosclerosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.121.316854","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T05:00:21Z","timestamp":1636606821000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":37,"title":["Macrophage LRP1 (Low-Density Lipoprotein Receptor-Related Protein 1) Is Required for the Effect of CD47 Blockade on Efferocytosis and Atherogenesis\u2014Brief Report"],"prefix":"10.1161","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9315-0152","authenticated-orcid":true,"given":"Paul A.","family":"Mueller","sequence":"first","affiliation":[{"name":"Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health &amp; Science University, Portland (P.A.M., K.T.H., R.A.M., H.T., N.P., S.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Kojima","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, Department of Surgery (Y.K., J.Y., N.J.L.), Stanford University School of Medicine, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine T.","family":"Huynh","sequence":"additional","affiliation":[{"name":"Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health &amp; Science University, Portland (P.A.M., K.T.H., R.A.M., H.T., N.P., S.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Maldonado","sequence":"additional","affiliation":[{"name":"Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health &amp; Science University, Portland (P.A.M., K.T.H., R.A.M., H.T., N.P., S.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4492-3897","authenticated-orcid":true,"given":"Jianqin","family":"Ye","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, Department of Surgery (Y.K., J.Y., N.J.L.), Stanford University School of Medicine, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagai","family":"Tavori","sequence":"additional","affiliation":[{"name":"Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health &amp; Science University, Portland (P.A.M., K.T.H., R.A.M., H.T., N.P., S.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2074-888X","authenticated-orcid":true,"given":"Nathalie","family":"Pamir","sequence":"additional","affiliation":[{"name":"Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health &amp; Science University, Portland (P.A.M., K.T.H., R.A.M., H.T., N.P., S.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0905-2806","authenticated-orcid":true,"given":"Nicholas J.","family":"Leeper","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, Department of Surgery (Y.K., J.Y., N.J.L.), Stanford University School of Medicine, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8145-8034","authenticated-orcid":true,"given":"Sergio","family":"Fazio","sequence":"additional","affiliation":[{"name":"Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health &amp; Science University, Portland (P.A.M., K.T.H., R.A.M., H.T., N.P., S.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2008.04.058"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.309229"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.025684"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2017.00086"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI90520"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature18935"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R800032-JLR200"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117619"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9896(2000)9999:9999<::AID-PATH699>3.0.CO;2-9"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0008-6363(99)00235-7"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.99.3.348"},{"key":"e_1_3_3_13_2","first-page":"281","article-title":"Apoptosis is associated with increased cell surface tissue factor procoagulant activity.","volume":"75","author":"Greeno EW","year":"1996","unstructured":"Greeno, EW, Bach, RR, Moldow, CF. Apoptosis is associated with increased cell surface tissue factor procoagulant activity. Lab Invest. 1996;75:281\u2013289.","journal-title":"Lab Invest"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00033.2007"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.202051"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72051"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000260204.40510.aa"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.032268"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21783"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.10.6366"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.05.046"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1121623109"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14802"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.307736"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATV.0000000000000062"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep35234"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12950-017-0151-x"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12968-y"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.108.11.3419"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-019-0619-3"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.302699"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008852"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3520"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0768-4"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.10.002"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.11.056"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.031702"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.29292"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M056689"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.306860"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI70391"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.01.001"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.121.316854","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T19:49:33Z","timestamp":1715543373000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.121.316854"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1161\/ATVBAHA.121.316854"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.121.316854","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1]]},"assertion":[{"value":"2020-08-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}