{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:24:09Z","timestamp":1790519049445,"version":"4.1.0"},"reference-count":74,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:p>\n                    Atherosclerosis, a disease of blood vessels, is driven by cholesterol accumulation and inflammation. Gene therapy that removes cholesterol from blood vessels and decreases inflammation is a promising approach for prevention and treatment of atherosclerosis. In previous work, we reported that helper-dependent adenoviral (HDAd) overexpression of apolipoprotein A-I (apoAI) in endothelial cells (ECs) increases cholesterol efflux\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and reduces atherosclerosis\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    . However, the effect of HDAdApoAI on atherosclerosis is partial. To improve this therapy, we considered concurrent overexpression of ATP-binding cassette subfamily A, member 1 (ABCA1), a protein that is required for apoAI-mediated cholesterol efflux. Before attempting combined apoAI\/ABCA1 gene therapy, we tested whether an HDAd that expresses ABCA1 (HDAdABCA1) increases EC cholesterol efflux, whether increased cholesterol efflux alters normal EC physiology, and whether ABCA1 overexpression in ECs has anti-inflammatory effects. HDAdABCA1 increased EC ABCA1 protein (\u223c3-fold;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and apoAI-mediated cholesterol efflux (2.3-fold;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.007). Under basal culture conditions, ABCA1 overexpression did not alter EC proliferation, metabolism, migration, apoptosis, nitric oxide production, or inflammatory gene expression. However, in serum-starved, apoAI-treated EC, ABCA1 overexpression had anti-inflammatory effects: decreased inflammatory gene expression (\u223c50%;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009\u2264\u20090.02 for interleukin [IL]-6, tumor necrosis factor [TNF]-\u03b1, and vascular cell adhesion protein-1); reduced lipid-raft Toll-like receptor 4 (80%;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.001); and a trend towards increased nitric oxide production (\u223c55%;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.1). In ECs stimulated with lipopolysaccharide, ABCA1 overexpression markedly decreased inflammatory gene expression (\u223c90% for IL-6 and TNF-\u03b1;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Therefore, EC ABCA1 overexpression has no toxic effects and counteracts the two key drivers of atherosclerosis: cholesterol accumulation and inflammation.\n                    <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                    testing of HDAdABCA1 is warranted.\n                  <\/jats:p>","DOI":"10.1089\/hum.2018.120","type":"journal-article","created":{"date-parts":[[2018,8,4]],"date-time":"2018-08-04T05:19:21Z","timestamp":1533359961000},"page":"236-248","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":62,"title":["ABCA1 Overexpression in Endothelial Cells\n                    <i>In Vitro<\/i>\n                    Enhances ApoAI-Mediated Cholesterol Efflux and Decreases Inflammation"],"prefix":"10.1177","volume":"30","author":[{"given":"Alexis","family":"Stamatikos","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Washington, Seattle, Washington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagadhara","family":"Dronadula","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Washington, Seattle, Washington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Knight","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Washington, Seattle, Washington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley K.","family":"Wacker","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Washington, Seattle, Washington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongren","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Washington, Seattle, Washington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Washington, Seattle, Washington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Dichek","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Washington, Seattle, 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