β-Adrenergic Blocker, Carvedilol, Abolishes Ameliorating Actions of Adipose-Derived Stem Cell Sheets on Cardiac Dysfunction and Remodeling After Myocardial Infarction

• Adachi Maya

  Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science

• Watanabe Mai

  Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science

• Kurata Yasutaka

  Department of Physiology II, Kanazawa Medical University Faculty of Medicine

• Inoue Yumiko

  Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science

• Notsu Tomomi

  Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science

• Yamamoto Kenshiro

  Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science

• Horie Hiromu

  Department of Cardiovascular Surgery, Tottori University Faculty of Medicine

• Tanno Shogo

  Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science

• Morita Maki

  Department of Plastic and Reconstructive Surgery, Tottori University Faculty of Medicine

• Miake Junichiro

  Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Tottori University Faculty of Medicine

• Hamada Toshihiro

  Department of Community-Based Family Medicine, Tottori University Faculty of Medicine

• Kuwabara Masanari

  Department of Cardiology, Toranomon Hospital

• Nakasone Naoe

  Department of Biological Regulation, Tottori University

• Ninomiya Haruaki

  Department of Biological Regulation, Tottori University

• Tsuneto Motokazu

  Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science

• Shirayoshi Yasuaki

  Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science

• Yoshida Akio

  Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science

• Nishimura Motonobu

  Department of Cardiovascular Surgery, Tottori University Faculty of Medicine

• Yamamoto Kazuhiro

  Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Tottori University Faculty of Medicine

• Hisatome Ichiro

  Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science

抄録

Background:Treatment of myocardial infarction (MI) includes inhibition of the sympathetic nervous system (SNS). Cell-based therapy using adipose-derived stem cells (ASCs) has emerged as a novel therapeutic approach to treat heart failure in MI. The purpose of this study was to determine whether a combination of ASC transplantation and SNS inhibition synergistically improves cardiac functions after MI. Methods and Results:ASCs were isolated from fat tissues of Lewis rats. In in vitro studies using cultured ASC cells, mRNA levels of angiogenic factors under normoxia or hypoxia, and the effects of norepinephrine and a β-blocker, carvedilol, on the mRNA levels were determined. Hypoxia increased vascular endothelial growth factor (VEGF) mRNA in ASCs. Norepinephrine further increased VEGF mRNA; this effect was unaffected by carvedilol. VEGF promoted VEGF receptor phosphorylation and tube formation of human umbilical vein endothelial cells, which were inhibited by carvedilol. In in vivo studies using a rat MI model, transplanted ASC sheets improved contractile functions of MI hearts; they also facilitated neovascularization and suppressed fibrosis after MI. These beneficial effects of ASC sheets were abolished by carvedilol. The effects of ASC sheets and carvedilol on MI heart functions were confirmed by Langendorff perfusion experiments using isolated hearts. Conclusions:ASC sheets prevented cardiac dysfunctions and remodeling after MI in a rat model via VEGF secretion. Inhibition of VEGF effects by carvedilol abolished their beneficial effects.

収録刊行物

• Circulation Journal

  Circulation Journal 83 (11), 2282-2291, 2019-10-25

  一般社団法人 日本循環器学会

キーワード

• Adipose-derived stem cells
• Adrenergic receptor blocker
• Carvedilol
• Cell sheet
• Myocardial infarction

詳細情報

• CRID: 1390001277373583232
• NII論文ID: 130007733310
• NII書誌ID: AA11591968
• DOI: 10.1253/circj.cj-19-0261
• ISSN: 13474820
• ISSN: 13469843
• NDL書誌ID: 030030582
• PubMed: 31527337
• Web Site: http://id.ndl.go.jp/bib/030030582
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I030030582
• Web Site: https://www.jstage.jst.go.jp/article/circj/83/11/83_CJ-19-0261/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2020233398
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可