{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:14:40Z","timestamp":1793142880060,"version":"4.5.0"},"reference-count":65,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2017,3,3]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Heart failure and atherosclerosis share the underlying mechanisms of chronic inflammation followed by fibrosis. A highly conserved microRNA (miR), miR-33, is considered as a potential therapeutic target for atherosclerosis because it regulates lipid metabolism and inflammation. However, the role of miR-33 in heart failure remains to be elucidated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>To clarify the role of miR-33 involved in heart failure.<\/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>We first investigated the expression levels of miR-33a\/b in human cardiac tissue samples with dilated cardiomyopathy. Increased expression of miR-33a was associated with improving hemodynamic parameters. To clarify the role of miR-33 in remodeling hearts, we investigated the responses to pressure overload by transverse aortic constriction in miR-33\u2013deficient (knockout [KO]) mice. When mice were subjected to transverse aortic constriction, miR-33 expression levels were significantly upregulated in wild-type left ventricles. There was no difference in hypertrophic responses between wild-type and miR-33KO hearts, whereas cardiac fibrosis was ameliorated in miR-33KO hearts compared with wild-type hearts. Despite the ameliorated cardiac fibrosis, miR-33KO mice showed impaired systolic function after transverse aortic constriction. We also found that cardiac fibroblasts were mainly responsible for miR-33 expression in the heart. Deficiency of miR-33 impaired cardiac fibroblast proliferation, which was considered to be caused by altered lipid raft cholesterol content. Moreover, cardiac fibroblast\u2013specific miR-33\u2013deficient mice also showed decreased cardiac fibrosis induced by transverse aortic constriction as systemic miR-33KO mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusion:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Our results demonstrate that miR-33 is involved in cardiac remodeling, and it preserves lipid raft cholesterol content in fibroblasts and maintains adaptive fibrotic responses in the remodeling heart.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.116.309528","type":"journal-article","created":{"date-parts":[[2016,12,6]],"date-time":"2016-12-06T03:40:24Z","timestamp":1480995624000},"page":"835-847","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":69,"title":["MicroRNA-33 Controls Adaptive Fibrotic Response in the Remodeling Heart by Preserving Lipid Raft Cholesterol"],"prefix":"10.1161","volume":"120","author":[{"given":"Masataka","family":"Nishiga","sequence":"first","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan (M.N., T.H., Y.K., O.B., T.Nakao, T.Nishino, D.H., Y.N., H.N., F.N., Y.I., S.K., M.K., R.H., T.Kimura, K.O.); Department of Cardiovascular Center, Osaka Red Cross Hospital, Japan (K.N., T.I.); Department of Pharmacology, Kansai Medical University, Hirakata, Osaka, Japan (T.Nakamura); Division of Translational Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Horie","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan (M.N., T.H., Y.K., O.B., T.Nakao, T.Nishino, D.H., Y.N., H.N., F.N., Y.I., S.K., M.K., R.H., T.Kimura, K.O.); Department of Cardiovascular Center, Osaka Red Cross Hospital, Japan (K.N., T.I.); Department of Pharmacology, Kansai Medical University, Hirakata, Osaka, Japan (T.Nakamura); Division of Translational Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhide","family":"Kuwabara","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan (M.N., T.H., Y.K., O.B., T.Nakao, T.Nishino, D.H., Y.N., H.N., F.N., Y.I., S.K., M.K., R.H., T.Kimura, K.O.); Department of Cardiovascular Center, Osaka Red Cross Hospital, Japan (K.N., T.I.); Department of Pharmacology, Kansai Medical University, Hirakata, Osaka, Japan (T.Nakamura); Division of Translational Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Nagao","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan (M.N., T.H., Y.K., O.B., T.Nakao, T.Nishino, D.H., Y.N., H.N., F.N., Y.I., S.K., M.K., R.H., T.Kimura, K.O.); Department of Cardiovascular Center, Osaka Red Cross Hospital, Japan (K.N., T.I.); Department of Pharmacology, Kansai Medical University, Hirakata, Osaka, Japan (T.Nakamura); Division of Translational Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Baba","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan (M.N., T.H., Y.K., O.B., T.Nakao, T.Nishino, D.H., Y.N., H.N., F.N., Y.I., S.K., M.K., R.H., T.Kimura, K.O.); Department of Cardiovascular Center, Osaka Red Cross Hospital, Japan (K.N., T.I.); Department of Pharmacology, Kansai Medical University, Hirakata, Osaka, Japan (T.Nakamura); Division of Translational Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsushi","family":"Nakao","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan (M.N., T.H., Y.K., O.B., T.Nakao, T.Nishino, D.H., Y.N., H.N., F.N., Y.I., S.K., M.K., R.H., T.Kimura, K.O.); Department of Cardiovascular Center, Osaka Red Cross Hospital, Japan (K.N., T.I.); Department of Pharmacology, Kansai Medical University, Hirakata, Osaka, Japan (T.Nakamura); Division of Translational Research, Clinical Research Institute, National Hospital Organization Kyoto Medical 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K.O.); Department of Cardiovascular Center, Osaka Red Cross Hospital, Japan (K.N., T.I.); Department of Pharmacology, Kansai Medical University, Hirakata, Osaka, Japan (T.Nakamura); Division of Translational Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Ide","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan (M.N., T.H., Y.K., O.B., T.Nakao, T.Nishino, D.H., Y.N., H.N., F.N., Y.I., S.K., M.K., R.H., T.Kimura, K.O.); Department of Cardiovascular Center, Osaka Red Cross Hospital, Japan (K.N., T.I.); Department of Pharmacology, Kansai Medical University, Hirakata, Osaka, Japan (T.Nakamura); Division of Translational Research, Clinical Research Institute, National Hospital Organization Kyoto Medical 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T.Kimura, K.O.); Department of Cardiovascular Center, Osaka Red Cross Hospital, Japan (K.N., T.I.); Department of Pharmacology, Kansai Medical University, Hirakata, Osaka, Japan (T.Nakamura); Division of Translational Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritsuko","family":"Hanada","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan (M.N., T.H., Y.K., O.B., T.Nakao, T.Nishino, D.H., Y.N., H.N., F.N., Y.I., S.K., M.K., R.H., T.Kimura, K.O.); Department of Cardiovascular Center, Osaka Red Cross Hospital, Japan (K.N., T.I.); Department of Pharmacology, Kansai Medical University, Hirakata, Osaka, Japan (T.Nakamura); Division of Translational Research, Clinical Research Institute, National Hospital Organization Kyoto Medical 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