{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:34:02Z","timestamp":1792154042688,"version":"4.4.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2008,10]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Objective\u2014<\/jats:italic>\n            <\/jats:bold>\n            The key initial step in atherogenesis is the subendothelial retention of apolipoprotein B\u2013containing lipoproteins. Acid sphingomyelinase (acid SMase), an enzyme present extracellularly within the arterial wall, strongly enhances lipoprotein retention in model systems in vitro, and retained lipoproteins in human plaques are enriched in ceramide, a product of SMase. We now sought to test a direct causative role for acid SMase in lipoprotein retention and atherogenesis in vivo.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            We studied atherogenesis and lipoprotein retention in\n            <jats:italic>Asm<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            versus\n            <jats:italic>Asm<\/jats:italic>\n            <jats:sup>+\/+<\/jats:sup>\n            mice on the\n            <jats:italic>Apoe<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            and\n            <jats:italic>Ldlr<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            backgrounds.\n            <jats:italic>Asm<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            ;\n            <jats:italic>Apoe<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice had a \u224840% to 50% decrease in early foam cell aortic root lesion area compared with\n            <jats:italic>Asm<\/jats:italic>\n            <jats:sup>+\/+<\/jats:sup>\n            ;\n            <jats:italic>Apoe<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05) despite no difference in plasma cholesterol or lipoproteins. To assay lipoprotein retention in vivo, the two groups of mice were injected with fluorescently labeled\n            <jats:italic>Apoe<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            lipoproteins. Early foam cell lesions of\n            <jats:italic>Asm<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            ;\n            <jats:italic>Apoe<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice showed a striking 87% reduction in lipoprotein trapping (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.0001) compared with\n            <jats:italic>Asm<\/jats:italic>\n            <jats:sup>+\/+<\/jats:sup>\n            ;\n            <jats:italic>Apoe<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            lesions. Similar results were obtained with\n            <jats:italic>Ldlr<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice, including an 81% reduction in lipoprotein retention within\n            <jats:italic>Asm<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            ;\n            <jats:italic>Ldlr<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            lesions compared with\n            <jats:italic>Asm<\/jats:italic>\n            <jats:sup>+\/+<\/jats:sup>\n            ;\n            <jats:italic>Ldlr<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            lesions (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.0005).\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            These findings support a causal role for acid SMase in lipoprotein retention and lesion progression and provides further support for the response-to-retention model of atherogenesis.\n          <\/jats:p>","DOI":"10.1161\/atvbaha.108.173344","type":"journal-article","created":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T02:04:00Z","timestamp":1217556240000},"page":"1723-1730","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":139,"title":["Acid Sphingomyelinase Promotes Lipoprotein Retention Within Early Atheromata and Accelerates Lesion Progression"],"prefix":"10.1161","volume":"28","author":[{"given":"Cecilia M.","family":"Devlin","sequence":"first","affiliation":[{"name":"From the Departments of Medicine (C.M.D., A.R.L., G.K., I.T.), Pathology &amp; Cell Biology (I.T.), and Physiology &amp; Cellular Biophysics (I.T.), Columbia University, New York; the Department of Genetics and Genomic Sciences (E.H.S.), Mount Sinai School of Medicine, New York; and the Division of Endocrinology, Diabetes, and Metabolic Diseases, Department of Medicine (K.J.W.), Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Leventhal","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (C.M.D., A.R.L., G.K., I.T.), Pathology &amp; Cell Biology (I.T.), and Physiology &amp; Cellular Biophysics (I.T.), Columbia University, New York; the Department of Genetics and Genomic Sciences (E.H.S.), Mount Sinai School of Medicine, New York; and the Division of Endocrinology, Diabetes, and Metabolic Diseases, Department of Medicine (K.J.W.), Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Kuriakose","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (C.M.D., A.R.L., G.K., I.T.), Pathology &amp; Cell Biology (I.T.), and Physiology &amp; Cellular Biophysics (I.T.), Columbia University, New York; the Department of Genetics and Genomic Sciences (E.H.S.), Mount Sinai School of Medicine, New York; and the Division of Endocrinology, Diabetes, and Metabolic Diseases, Department of Medicine (K.J.W.), Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward H.","family":"Schuchman","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (C.M.D., A.R.L., G.K., I.T.), Pathology &amp; Cell Biology (I.T.), and Physiology &amp; Cellular Biophysics (I.T.), Columbia University, New York; the Department of Genetics and Genomic Sciences (E.H.S.), Mount Sinai School of Medicine, New York; and the Division of Endocrinology, Diabetes, and Metabolic Diseases, Department of Medicine (K.J.W.), Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin Jon","family":"Williams","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (C.M.D., A.R.L., G.K., I.T.), Pathology &amp; Cell Biology (I.T.), and Physiology &amp; Cellular Biophysics (I.T.), Columbia University, New York; the Department of Genetics and Genomic Sciences (E.H.S.), Mount Sinai School of Medicine, New York; and the Division of Endocrinology, Diabetes, and Metabolic Diseases, Department of Medicine (K.J.W.), Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Tabas","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (C.M.D., A.R.L., G.K., I.T.), Pathology &amp; Cell Biology (I.T.), and Physiology &amp; Cellular Biophysics (I.T.), Columbia University, New York; the Department of Genetics and Genomic Sciences (E.H.S.), Mount Sinai School of Medicine, New York; and the Division of Endocrinology, Diabetes, and Metabolic Diseases, Department of Medicine (K.J.W.), Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.15.5.551"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.676890"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-003-3262-x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)42610-0"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00804"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.29.18250"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.7.4081"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.150098097"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.5.2738"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.20.12.2607"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.mol.0000245259.63505.c2"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118934"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.15.4.534"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000168912.42941.60"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)80745-5"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.19.11.2648"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.20.12.2614"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwj140"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412348200"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0795-288"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.9.6.895"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/atv91.14.1.8274468"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/atv91.14.1.8274470"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24327"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.9.6.908"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.107.149666"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M700329-JLR200"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106455200"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2004.02.048"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.108.173344","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:14:57Z","timestamp":1715555697000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.108.173344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10]]},"references-count":29,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2008,10]]}},"alternative-id":["10.1161\/ATVBAHA.108.173344"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.108.173344","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10]]},"assertion":[{"value":"2008-07-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}