{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:05:38Z","timestamp":1791223538885,"version":"4.1.0"},"reference-count":69,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Enzyme-modified nonoxidized low-density lipoprotein (ELDL) is present in human atherosclerotic lesions. Our objective is to understand the mechanisms of ELDL uptake and its effects on vascular smooth muscle cells (SMC).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Transformation of murine aortic SMCs into foam cells in response to ELDL was analyzed. ELDL, but not acetylated or oxidized LDL, was potent in inducing SMC foam cell formation. Inhibitors of macropinocytosis (LY294002, wortmannin, amiloride) attenuated ELDL uptake. In contrast, inhibitors of receptor-mediated endocytosis (dynasore, sucrose) and inhibitor of caveolae-\/lipid raft\u2013mediated endocytosis (filipin) had no effect on ELDL uptake in SMC, suggesting that macropinocytosis is the main mechanism of ELDL uptake by SMC. Receptor for advanced glycation end products (RAGE) is not obligatory for ELDL-induced SMC foam cell formation, but primes SMC for the uptake of oxidized LDL in a RAGE-dependent manner. ELDL increased intracellular reactive oxygen species, cytosolic calcium, and expression of lectin-like oxidized LDL receptor-1 in wild-type SMC but not in RAGE\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              SMC. The macropinocytotic uptake of ELDL is regulated predominantly by intracellular calcium because ELDL uptake was completely inhibited by pretreatment with the calcium channel inhibitor lacidipine in wild-type and RAGE\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              SMC. This is in contrast to pretreatment with PI3 kinase inhibitors which completely prevented ELDL uptake in RAGE\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              SMC, but only partially in wild-type SMC.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>ELDL is highly potent in inducing foam cells in murine SMC. ELDL endocytosis is mediated by calcium-dependent macropinocytosis. Priming SMC with ELDL enhances the uptake of oxidized LDL.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.116.307306","type":"journal-article","created":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T02:59:39Z","timestamp":1460689179000},"page":"1101-1113","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":73,"title":["Enzymatically Modified Low-Density Lipoprotein Promotes Foam Cell Formation in Smooth Muscle Cells via Macropinocytosis and Enhances Receptor-Mediated Uptake of Oxidized Low-Density Lipoprotein"],"prefix":"10.1161","volume":"36","author":[{"given":"Bijoy","family":"Chellan","sequence":"first","affiliation":[{"name":"From the Department of Medicine (B.C., M.A.H.B.), and Department of Pathology (C.A.R., G.S.G), University of Chicago, IL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A.","family":"Reardon","sequence":"additional","affiliation":[{"name":"From the Department of Medicine (B.C., M.A.H.B.), and Department of Pathology (C.A.R., G.S.G), University of Chicago, IL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Godfrey S.","family":"Getz","sequence":"additional","affiliation":[{"name":"From the Department of Medicine (B.C., M.A.H.B.), and Department of Pathology (C.A.R., G.S.G), University of Chicago, IL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion A.","family":"Hofmann Bowman","sequence":"additional","affiliation":[{"name":"From the Department of Medicine (B.C., M.A.H.B.), and Department of Pathology (C.A.R., G.S.G), University of Chicago, IL."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn099"},{"key":"e_1_3_5_3_2","first-page":"402","article-title":"Intimal cells and atherosclerosis. Relationship between the number of intimal cells and major manifestations of atherosclerosis in the human aorta.","volume":"125","author":"Orekhov AN","year":"1986","unstructured":"Orekhov AN, Andreeva ER, Krushinsky AV, Novikov ID, Tertov VV, Nestaiko GV, Khashimov KhA, Repin VS, Smirnov VN. Intimal cells and atherosclerosis. Relationship between the number of intimal cells and major manifestations of atherosclerosis in the human aorta. Am J Pathol. 1986;125:402\u2013415.","journal-title":"Am J Pathol"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(98)00318-6"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.04.005"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0802498"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.23.17661"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42823"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1735526100"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.841130"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.005015"},{"key":"e_1_3_5_12_2","first-page":"907","article-title":"Human atherosclerosis. III. Immunocytochemical analysis of the cell composition of lesions of young adults.","volume":"140","author":"Katsuda S","year":"1992","unstructured":"Katsuda S, Boyd HC, Fligner C, Ross R, Gown AM. Human atherosclerosis. III. Immunocytochemical analysis of the cell composition of lesions of young adults. Am J Pathol. 1992;140:907\u2013914.","journal-title":"Am J Pathol"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.23.2307"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.304029"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003337200"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)32377-4"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)30183-8"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1035"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000148202.49842.3b"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.1.82"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.15.1799"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.6.1959"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.18.3.369"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.21.6.1004"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000063614.21233.BF"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(76)90189-2"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000077207.49221.06"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808650105"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01765.x"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000144016.85221.66"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI14915"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310814200"},{"key":"e_1_3_5_33_2","first-page":"125","article-title":"Chymase-containing mast cells in human arterial intima: implications for atherosclerotic disease.","author":"Kovanen PT","year":"1997","unstructured":"Kovanen PT. Chymase-containing mast cells in human arterial intima: implications for atherosclerotic disease. Heart Vessels. 1997;suppl 12:125\u2013127.","journal-title":"Heart Vessels"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/386073a0"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.101105"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/11.suppl_E.72"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.24.11603"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)31999-4"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612054865064"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.020917"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1206751"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.212217"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-7-17"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-178-9_2"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2006.04.002"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03238"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.134015"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201309081"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2012.891"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000167522.48370.5e"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6102-11.2012"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026398310003"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200908086"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201412052"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118596"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E09-07-0559"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.17.5.969"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.37.21672"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117628"},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407167200"},{"key":"e_1_3_5_62_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.11.7495"},{"key":"e_1_3_5_63_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000039288.86470.dd"},{"key":"e_1_3_5_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12360"},{"key":"e_1_3_5_65_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2005.tb00337.x"},{"key":"e_1_3_5_66_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20120873"},{"key":"e_1_3_5_67_2","doi-asserted-by":"publisher","DOI":"10.25011\/cim.v35i5.18701"},{"key":"e_1_3_5_68_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-13-78"},{"key":"e_1_3_5_69_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp036"},{"key":"e_1_3_5_70_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32703"},{"key":"e_1_3_5_71_2","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1808"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.116.307306","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:09:04Z","timestamp":1715555344000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.116.307306"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6]]},"references-count":69,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["10.1161\/ATVBAHA.116.307306"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.116.307306","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6]]},"assertion":[{"value":"2015-10-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-03-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-04-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}