{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:50:36Z","timestamp":1792799436024,"version":"4.5.0"},"reference-count":57,"publisher":"Wiley","license":[{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Heart Foundation of Australia Career Development Award","award":["CR 12S 6833"],"award-info":[{"award-number":["CR 12S 6833"]}],"id":[{"id":"https:\/\/ror.org\/039d9wr27","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Heart Foundation of Australia Career Development Award","award":["GNT1037074"],"award-info":[{"award-number":["GNT1037074"]}],"id":[{"id":"https:\/\/ror.org\/039d9wr27","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["CR 12S 6833"],"award-info":[{"award-number":["CR 12S 6833"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1037074"],"award-info":[{"award-number":["GNT1037074"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Diabetes Research"],"published-print":{"date-parts":[[2021,5,6]]},"abstract":"<jats:p>Background and Aims. Apolipoprotein A-I (ApoA-I), the main component of high-density lipoprotein (HDL), not only promotes reverse cholesterol transport (RCT) in atherosclerosis but also increases insulin secretion in pancreatic \u03b2-cells, suggesting that interventions which raise HDL levels may be beneficial in diabetes-associated cardiovascular disease (CVD). Previously, we showed that TNF-related apoptosis-inducing ligand (TRAIL) deletion in Apolipoprotein Eknockout (Apoe-\/-) mice results in diabetes-accelerated atherosclerosis in response to a \u201cWestern\u201d diet. Here, we sought to identify whether reconstituted HDL (rHDL) could improve features of diabetes-associated CVD in Trail-\/-Apoe-\/- mice. Methods and Results. Trail-\/-Apoe-\/- and Apoe-\/- mice on a \u201cWestern\u201d diet for 12\u2009weeks received 3 weekly infusions of either PBS (vehicle) or rHDL (containing ApoA-I (20\u2009mg\/kg) and 1-palmitoyl-2-linoleoyl phosphatidylcholine). Administration of rHDL reduced total plasma cholesterol, triglyceride, and glucose levels in Trail-\/-Apoe-\/- but not in Apoe-\/- mice, with no change in weight gain observed. rHDL treatment also improved glucose clearance in response to insulin and glucose tolerance tests. Immunohistological analysis of pancreata revealed increased insulin expression\/production and a reduction in macrophage infiltration in mice with TRAIL deletion. Furthermore, atherosclerotic plaque size in Trail-\/-Apoe-\/- mice was significantly reduced associating with increased expression of the M2 macrophage marker CD206, suggesting HDL's involvement in the polarization of macrophages. rHDL also increased vascular mRNA expression of RCT transporters, ABCA1 and ABCG1, in Trail-\/-Apoe-\/- but not in Apoe-\/- mice. Conclusions. rHDL improves features of diabetes-associated atherosclerosis in mice. These findings support the therapeutic potential of rHDL in the treatment of atherosclerosis and associated diabetic complications. More studies are warranted to understand rHDL\u2019s mechanism of action.<\/jats:p>","DOI":"10.1155\/2021\/6668506","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T11:05:05Z","timestamp":1621595105000},"page":"1-10","source":"Crossref","is-referenced-by-count":42,"title":["HDL Improves Cholesterol and Glucose Homeostasis and Reduces Atherosclerosis in Diabetes-Associated Atherosclerosis"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8420-0461","authenticated-orcid":true,"given":"Belinda A.","family":"Di Bartolo","sequence":"first","affiliation":[{"name":"The University of Sydney, Kolling Institute of Medical Research, Sydney, Australia"},{"name":"Faculty of Medicine and Health, Sydney, Australia"},{"name":"Heart Research Institute, Sydney, Australia"},{"name":"The University of New South Wales, Faculty of Medicine, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1723-2679","authenticated-orcid":true,"given":"Si\u00e2n P.","family":"Cartland","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health, Sydney, Australia"},{"name":"Heart Research Institute, Sydney, Australia"},{"name":"The University of New South Wales, Faculty of Medicine, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Genner","sequence":"additional","affiliation":[{"name":"Heart Research Institute, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep","family":"Manuneedhi Cholan","sequence":"additional","affiliation":[{"name":"Heart Research Institute, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Vellozzi","sequence":"additional","affiliation":[{"name":"Heart Research Institute, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9751-917X","authenticated-orcid":true,"given":"Kerry-Anne","family":"Rye","sequence":"additional","affiliation":[{"name":"The University of New South Wales, Faculty of Medicine, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7353-0932","authenticated-orcid":true,"given":"Mary M.","family":"Kavurma","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health, Sydney, Australia"},{"name":"Heart Research Institute, Sydney, Australia"},{"name":"The University of New South Wales, Faculty of Medicine, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-6-35"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-1364"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000434"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.2337\/db16-0046"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-008-0975-2"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.143875"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114558"},{"issue":"3","key":"8","first-page":"455","article-title":"High density lipoprotein plasma fractions inhibit aortic fatty streaks in cholesterol-fed rabbits","volume":"60","author":"J. 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