{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T23:10:52Z","timestamp":1790464252939,"version":"4.1.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2015,7,17]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>Therapeutically targeting macrophage reverse cholesterol transport is a promising approach to treat atherosclerosis. Macrophage energy metabolism can significantly influence macrophage phenotype, but how this is controlled in foam cells is not known. Bioinformatic pathway analysis predicts that miR-33 represses a cluster of genes controlling cellular energy metabolism that may be important in macrophage cholesterol efflux.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>We hypothesized that cellular energy status can influence cholesterol efflux from macrophages, and that miR-33 reduces cholesterol efflux via repression of mitochondrial energy metabolism pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Methods and Results:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      In this study, we demonstrated that macrophage cholesterol efflux is regulated by mitochondrial ATP production, and that miR-33 controls a network of genes that synchronize mitochondrial function. Inhibition of mitochondrial ATP synthase markedly reduces macrophage cholesterol efflux capacity, and anti-miR33 required fully functional mitochondria to enhance ABCA1-mediated cholesterol efflux. Specifically, anti-miR33 derepressed the novel target genes PGC-1\u03b1, PDK4, and SLC25A25 and boosted mitochondrial respiration and production of ATP. Treatment of atherosclerotic\n                      <jats:italic>Apoe<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice with anti-miR33 oligonucleotides reduced aortic sinus lesion area compared with controls, despite no changes in high-density lipoprotein cholesterol or other circulating lipids. Expression of miR-33a\/b was markedly increased in human carotid atherosclerotic plaques compared with normal arteries, and there was a concomitant decrease in mitochondrial regulatory genes PGC-1\u03b1, SLC25A25, NRF1, and TFAM, suggesting these genes are associated with advanced atherosclerosis in humans.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>This study demonstrates that anti-miR33 therapy derepresses genes that enhance mitochondrial respiration and ATP production, which in conjunction with increased ABCA1 expression, works to promote macrophage cholesterol efflux and reduce atherosclerosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.117.305624","type":"journal-article","created":{"date-parts":[[2015,5,22]],"date-time":"2015-05-22T20:18:51Z","timestamp":1432325931000},"page":"266-278","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":183,"title":["Macrophage Mitochondrial Energy Status Regulates Cholesterol Efflux and Is Enhanced by Anti-miR33 in Atherosclerosis"],"prefix":"10.1161","volume":"117","author":[{"given":"Denuja","family":"Karunakaran","sequence":"first","affiliation":[{"name":"From the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Brianne","family":"Thrush","sequence":"additional","affiliation":[{"name":"From the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"My-Anh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"From the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Richards","sequence":"additional","affiliation":[{"name":"From the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Geoffrion","sequence":"additional","affiliation":[{"name":"From the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ragunath","family":"Singaravelu","sequence":"additional","affiliation":[{"name":"From the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. 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Charney Division of Cardiology, New York University School of Medicine (M.O., K..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakriti","family":"Shangari","sequence":"additional","affiliation":[{"name":"From the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. 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Charney Division of Cardiology, New York University School of Medicine (M.O., K..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Maegdefessel","sequence":"additional","affiliation":[{"name":"From the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. 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