MicroRNA-33 Controls Adaptive Fibrotic Response in the Remodeling Heart by Preserving Lipid Raft Cholesterol
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- Masataka Nishiga
- 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,...
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- Takahiro Horie
- 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,...
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- Yasuhide Kuwabara
- 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,...
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- Kazuya Nagao
- 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,...
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- Osamu Baba
- 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,...
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- Tetsushi Nakao
- 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,...
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- Tomohiro Nishino
- 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,...
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- Daihiko Hakuno
- 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,...
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- Yasuhiro Nakashima
- 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,...
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- Hitoo Nishi
- 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,...
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- Fumiko Nakazeki
- 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,...
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- Yuya Ide
- 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,...
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- Satoshi Koyama
- 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,...
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- Masahiro Kimura
- 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,...
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- Ritsuko Hanada
- 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,...
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- Tomoyuki Nakamura
- 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,...
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- Tsukasa Inada
- 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,...
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- Koji Hasegawa
- 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,...
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- Simon J. Conway
- 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,...
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- Toru Kita
- 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,...
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- Takeshi Kimura
- 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,...
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- Koh Ono
- 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,...
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説明
<jats:sec> <jats:title> <jats:underline>Rationale:</jats:underline> </jats:title> <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> </jats:sec> <jats:sec> <jats:title> <jats:underline>Objective:</jats:underline> </jats:title> <jats:p>To clarify the role of miR-33 involved in heart failure.</jats:p> </jats:sec> <jats:sec> <jats:title> <jats:underline>Methods and Results:</jats:underline> </jats:title> <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–deficient (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–specific miR-33–deficient mice also showed decreased cardiac fibrosis induced by transverse aortic constriction as systemic miR-33KO mice.</jats:p> </jats:sec> <jats:sec> <jats:title> <jats:underline>Conclusion:</jats:underline> </jats:title> <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> </jats:sec>
収録刊行物
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- Circulation Research
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Circulation Research 120 (5), 835-847, 2017-03-03
Ovid Technologies (Wolters Kluwer Health)