{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T04:11:53Z","timestamp":1781151113033,"version":"3.54.1"},"reference-count":44,"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":[[2015,10]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Oxidative stress associated with cardiovascular disease can produce various oxidized lipids, including cholesterol oxides, such as 7-hydroperoxide (7-OOH), 7-hydroxide (7-OH), and 7-ketone (7=O). Unlike 7=O and 7-OH, 7-OOH is redox active, giving rise to the others via potentially toxic-free radical reactions. We tested the novel hypothesis that under oxidative stress conditions, steroidogenic acute regulatory (StAR) family proteins not only deliver cholesterol to\/into mitochondria of vascular macrophages, but also 7-OOH, which induces peroxidative damage that impairs early stage reverse cholesterol transport.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>Stimulation of human monocyte-derived THP-1 macrophages with dibutyryl-cAMP resulted in substantial upregulation of StarD1 and ATP-binding cassette (ABC) transporter, ABCA1. Small interfering RNA\u2013induced StarD1 knockdown before stimulation had no effect on StarD4, but reduced ABCA1 upregulation, linking the latter to StarD1 functionality. Mitochondria in stimulated StarD1-knockdown cells internalized 7-OOH slower than nonstimulated controls and underwent less 7-OOH\u2013induced lipid peroxidation and membrane depolarization, as probed with C11-BODIPY (4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-inda-cene-3-undecanoic acid) and JC-1 (5,5\u2032,6,6\u2032-tetrachloro-1,1\u2032,3,3\u2032-tetraethyl-benzimidazolylcarbocyanine iodide), respectively. Major functional consequences of 7-OOH exposure were (1) loss of mitochondrial CYP27A1 activity, (2) reduced 27-hydroxycholesterol (27-OH) output, and (3) downregulation of cholesterol-exporting ABCA1 and ABCG1. Consistently, 7-OOH\u2013challenged macrophages exported less cholesterol to apoA-I or high-density lipoprotein than did nonchallenged controls. StarD1-mediated 7-OOH transport was also found to be highly cytotoxic, whereas 7=O and 7-OH were minimally toxic.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>This study describes a previously unrecognized mechanism by which macrophage cholesterol efflux can be incapacitated under oxidative stress\u2013linked disorders, such as chronic obesity and hypertension. Our findings provide new insights into the role of macrophage redox damage\/dysfunction in atherogenesis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.115.306210","type":"journal-article","created":{"date-parts":[[2015,8,28]],"date-time":"2015-08-28T03:14:10Z","timestamp":1440731650000},"page":"2104-2113","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":47,"title":["Impairment of Macrophage Cholesterol Efflux by Cholesterol Hydroperoxide Trafficking"],"prefix":"10.1161","volume":"35","author":[{"given":"Witold","family":"Korytowski","sequence":"first","affiliation":[{"name":"From the Department of Biochemistry (A.W.G., W.K., D.S., A.C.C., J.C.S.) and Department of Medicine (D.S.), Medical College of Wisconsin, Milwaukee; and Department of Biophysics, Jagiellonian University, Krakow, Poland (W.K., K.W., P.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Wawak","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry (A.W.G., W.K., D.S., A.C.C., J.C.S.) and Department of Medicine (D.S.), Medical College of Wisconsin, Milwaukee; and Department of Biophysics, Jagiellonian University, Krakow, Poland (W.K., K.W., P.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Pabisz","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry (A.W.G., W.K., D.S., A.C.C., J.C.S.) and Department of Medicine (D.S.), Medical College of Wisconsin, Milwaukee; and Department of Biophysics, Jagiellonian University, Krakow, Poland (W.K., K.W., P.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared C.","family":"Schmitt","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry (A.W.G., W.K., D.S., A.C.C., J.C.S.) and Department of Medicine (D.S.), Medical College of Wisconsin, Milwaukee; and Department of Biophysics, Jagiellonian University, Krakow, Poland (W.K., K.W., P.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra C.","family":"Chadwick","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry (A.W.G., W.K., D.S., A.C.C., J.C.S.) and Department of Medicine (D.S.), Medical College of Wisconsin, Milwaukee; and Department of Biophysics, Jagiellonian University, Krakow, Poland (W.K., K.W., P.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy","family":"Sahoo","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry (A.W.G., W.K., D.S., A.C.C., J.C.S.) and Department of Medicine (D.S.), Medical College of Wisconsin, Milwaukee; and Department of Biophysics, Jagiellonian University, Krakow, Poland (W.K., K.W., P.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert W.","family":"Girotti","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry (A.W.G., W.K., D.S., A.C.C., J.C.S.) and Department of Medicine (D.S.), Medical College of Wisconsin, Milwaukee; and Department of Biophysics, Jagiellonian University, Krakow, Poland (W.K., K.W., P.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198904063201407"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)53430-X"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01370.x"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3520"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/07853890310008198"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.475715"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hci136"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2007.01898.x"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-007-6133-3"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2008.09.006"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2009.02.042"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212780200"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.8.4245"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32057"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2006.04.012"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0b013e32833dedaa"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.42.26253"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.24.11452"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)37566-0"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)37148-0"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2009.02.005"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-10-0860"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2012.12.001"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)32182-9"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.5551\/jat1994.1.80"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/131.11.2916"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.12.165"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2013.10.051"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20120358"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(02)00848-1"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2490095"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R300003200"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2007.02.012"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.452151"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/75192"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M022061"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(95)05594-M"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(89)90136-6"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.14.7.1177"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)40252-4"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-1097.1999.tb08242.x"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi960522k"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2002.tb02098.x"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23148"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.115.306210","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T18:08:30Z","timestamp":1727287710000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.115.306210"}},"subtitle":["Implications for Atherogenesis Under Oxidative Stress"],"short-title":[],"issued":{"date-parts":[[2015,10]]},"references-count":44,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2015,10]]}},"alternative-id":["10.1161\/ATVBAHA.115.306210"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.115.306210","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10]]},"assertion":[{"value":"2015-07-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-08-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-08-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}