MicroRNA-33 Controls Adaptive Fibrotic Response in the Remodeling Heart by Preserving Lipid Raft Cholesterol

  • 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,...
  • 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,...
  • 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,...
  • 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,...
  • 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,...
  • 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,...
  • 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,...
  • 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,...
  • 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,...
  • 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,...
  • 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,...
  • 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,...
  • 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,...
  • 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,...
  • 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,...
  • 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,...
  • 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,...
  • 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,...
  • 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,...
  • 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,...
  • 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,...
  • 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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<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

  • Circulation Research

    Circulation Research 120 (5), 835-847, 2017-03-03

    Ovid Technologies (Wolters Kluwer Health)

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参考文献 (65)*注記

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