{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:37:02Z","timestamp":1792427822957,"version":"4.5.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11_suppl_1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2012,9,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>MicroRNA are essential posttranscriptional modulators of gene expression implicated in various chronic diseases. Because microRNA-145 is highly expressed in vascular smooth muscle cells (VSMC) and regulates VSMC fate and plasticity, we hypothesized that it may be a novel regulator of atherosclerosis and plaque stability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>\n                      Apolipoprotein E knockout mice (\n                      <jats:italic>ApoE<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) mice were treated with either a microRNA-145 lentivirus under the control of the smooth muscle cell (SMC)-specific promoter\n                      <jats:italic>SM22<\/jats:italic>\n                      \u03b1 or a\n                      <jats:italic>SM22<\/jats:italic>\n                      \u03b1 control lentivirus before commencing the Western diet for 12 weeks. The SMC-targeted microRNA-145 treatment markedly reduced plaque size in aortic sinuses, ascending aortas, and brachiocephalic arteries. It also significantly increased fibrous cap area, reduced necrotic core area, and increased plaque collagen content. Cellular plaque composition analyses revealed significantly less macrophages in\n                      <jats:italic>ApoE<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice treated with the SMC-specific microRNA-145. These mice also demonstrated marked increases in calponin levels and \u03b1-smooth muscle actin\u2013positive SMC areas in their atherosclerotic lesions. Furthermore, lentiviral delivery of microRNA-145 resulted in reduced KLF4 and elevated myocardin expression in aortas from\n                      <jats:italic>ApoE<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice, consistent with an effect of microRNA-145 to promote a contractile phenotype in VSMC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>VSMC-specific overexpression of microRNA-145 is a novel in vivo therapeutic target to limit atherosclerotic plaque morphology and cellular composition, shifting the balance toward plaque stability vs plaque rupture.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.111.084186","type":"journal-article","created":{"date-parts":[[2012,9,10]],"date-time":"2012-09-10T16:34:09Z","timestamp":1347294849000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":225,"title":["MicroRNA-145 Targeted Therapy Reduces Atherosclerosis"],"prefix":"10.1161","volume":"126","author":[{"given":"Fina","family":"Lovren","sequence":"first","affiliation":[{"name":"From the Divisions of Cardiac Surgery (F.L., Y.P., A.Q., K.K.S., P.C.S., M.G., H.T., S.V.) and Nephrology (B.M.S., P.A.M.), Keenan Research Centre (F.L., Y.P., A.Q., K.K.S, P.C.S., B.M.S., M.G., M.A., H.T., P.A.M., S.V.), Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada; Departments of Medicine (M.G., P.A.M.) and Surgery (S.V.), University of Toronto, Toronto, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada (N.G., A.J.I., M.G..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Pan","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiac Surgery (F.L., Y.P., A.Q., K.K.S., P.C.S., M.G., H.T., S.V.) and Nephrology (B.M.S., P.A.M.), Keenan Research Centre (F.L., Y.P., A.Q., K.K.S, P.C.S., B.M.S., M.G., M.A., H.T., P.A.M., S.V.), Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada; Departments of Medicine (M.G., P.A.M.) and Surgery (S.V.), University of Toronto, Toronto, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada (N.G., A.J.I., M.G..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Quan","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiac Surgery (F.L., Y.P., A.Q., K.K.S., P.C.S., M.G., H.T., S.V.) and Nephrology (B.M.S., P.A.M.), Keenan Research Centre (F.L., Y.P., A.Q., K.K.S, P.C.S., B.M.S., M.G., M.A., H.T., P.A.M., S.V.), Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada; Departments of Medicine (M.G., P.A.M.) and Surgery (S.V.), University of Toronto, Toronto, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada (N.G., A.J.I., M.G..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna K.","family":"Singh","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiac Surgery (F.L., Y.P., A.Q., K.K.S., P.C.S., M.G., H.T., S.V.) and Nephrology (B.M.S., P.A.M.), Keenan Research Centre (F.L., Y.P., A.Q., K.K.S, P.C.S., B.M.S., M.G., M.A., H.T., P.A.M., S.V.), Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada; Departments of Medicine (M.G., P.A.M.) and Surgery (S.V.), University of Toronto, Toronto, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada (N.G., A.J.I., M.G..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praphulla C.","family":"Shukla","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiac Surgery (F.L., Y.P., A.Q., K.K.S., P.C.S., M.G., H.T., S.V.) and Nephrology (B.M.S., P.A.M.), Keenan Research Centre (F.L., Y.P., A.Q., K.K.S, P.C.S., B.M.S., M.G., M.A., H.T., P.A.M., S.V.), Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada; Departments of Medicine (M.G., P.A.M.) and Surgery (S.V.), University of Toronto, Toronto, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada (N.G., A.J.I., M.G..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandini","family":"Gupta","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiac Surgery (F.L., Y.P., A.Q., K.K.S., P.C.S., M.G., H.T., S.V.) and Nephrology (B.M.S., P.A.M.), Keenan Research Centre (F.L., Y.P., A.Q., K.K.S, P.C.S., B.M.S., M.G., M.A., H.T., P.A.M., S.V.), Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada; Departments of Medicine (M.G., P.A.M.) and Surgery (S.V.), University of Toronto, Toronto, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada (N.G., A.J.I., M.G..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent M.","family":"Steer","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiac Surgery (F.L., Y.P., A.Q., K.K.S., P.C.S., M.G., H.T., S.V.) and Nephrology (B.M.S., P.A.M.), Keenan Research Centre (F.L., Y.P., A.Q., K.K.S, P.C.S., B.M.S., M.G., M.A., H.T., P.A.M., S.V.), Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada; Departments of Medicine (M.G., P.A.M.) and Surgery (S.V.), University of Toronto, Toronto, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada (N.G., A.J.I., M.G..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair J.","family":"Ingram","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiac Surgery (F.L., Y.P., A.Q., K.K.S., P.C.S., M.G., H.T., S.V.) and Nephrology (B.M.S., P.A.M.), Keenan Research Centre (F.L., Y.P., A.Q., K.K.S, P.C.S., B.M.S., M.G., M.A., H.T., P.A.M., S.V.), Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada; Departments of Medicine (M.G., P.A.M.) and Surgery (S.V.), University of Toronto, Toronto, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada (N.G., A.J.I., M.G..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Gupta","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiac Surgery (F.L., Y.P., A.Q., K.K.S., P.C.S., M.G., H.T., S.V.) and Nephrology (B.M.S., P.A.M.), Keenan Research Centre (F.L., Y.P., A.Q., K.K.S, P.C.S., B.M.S., M.G., M.A., H.T., P.A.M., S.V.), Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada; Departments of Medicine (M.G., P.A.M.) and Surgery (S.V.), University of Toronto, Toronto, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada (N.G., A.J.I., M.G..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Al-Omran","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiac Surgery (F.L., Y.P., A.Q., K.K.S., P.C.S., M.G., H.T., S.V.) and Nephrology (B.M.S., P.A.M.), Keenan Research Centre (F.L., Y.P., A.Q., K.K.S, P.C.S., B.M.S., M.G., M.A., H.T., P.A.M., S.V.), Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada; Departments of Medicine (M.G., P.A.M.) and Surgery (S.V.), University of Toronto, Toronto, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada (N.G., A.J.I., M.G..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwee","family":"Teoh","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiac Surgery (F.L., Y.P., A.Q., K.K.S., P.C.S., M.G., H.T., S.V.) and Nephrology (B.M.S., P.A.M.), Keenan Research Centre (F.L., Y.P., A.Q., K.K.S, P.C.S., B.M.S., M.G., M.A., H.T., P.A.M., S.V.), Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada; Departments of Medicine (M.G., P.A.M.) and Surgery (S.V.), University of Toronto, Toronto, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada (N.G., A.J.I., M.G..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip A.","family":"Marsden","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiac Surgery (F.L., Y.P., A.Q., K.K.S., P.C.S., M.G., H.T., S.V.) and Nephrology (B.M.S., P.A.M.), Keenan Research Centre (F.L., Y.P., A.Q., K.K.S, P.C.S., B.M.S., M.G., M.A., H.T., P.A.M., S.V.), Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada; Departments of Medicine (M.G., P.A.M.) and Surgery (S.V.), University of Toronto, Toronto, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada (N.G., A.J.I., M.G..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subodh","family":"Verma","sequence":"additional","affiliation":[{"name":"From the Divisions of Cardiac Surgery (F.L., Y.P., A.Q., K.K.S., P.C.S., M.G., H.T., S.V.) and Nephrology (B.M.S., P.A.M.), Keenan Research Centre (F.L., Y.P., A.Q., K.K.S, P.C.S., B.M.S., M.G., M.A., H.T., P.A.M., S.V.), Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada; Departments of Medicine (M.G., P.A.M.) and Surgery (S.V.), University of Toronto, Toronto, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada (N.G., A.J.I., M.G..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01323"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/83.2.456S"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.110.210831"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00238-0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.105.570358"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.159327"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000250095"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00045-5"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00146.2010"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.109.200873"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.110.958702"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38864"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08195"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.8.21.9837"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.109.197517"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.106.141986"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2009.153"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1459"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.122.8.2415"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-11-4358"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-4120"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2006.127"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2010.07.002"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.10.007"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302348"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1997"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2006.09.009"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.09.029"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2007.02.006"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1064023"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.002"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.082701.108"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003420"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2441"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.132.5.849"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.111.084186","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T02:44:30Z","timestamp":1715568270000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.111.084186"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,11]]},"references-count":35,"journal-issue":{"issue":"11_suppl_1","published-print":{"date-parts":[[2012,9,11]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.111.084186"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.111.084186","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,9,11]]},"assertion":[{"value":"2012-09-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}