Sirt7 Deficiency Attenuates Neointimal Formation Following Vascular Injury by Modulating Vascular Smooth Muscle Cell Proliferation

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  • Kimura Yuichi
    Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University
  • Izumiya Yasuhiro
    Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine
  • Araki Satoshi
    Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University
  • Yamamura Satoru
    Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University
  • Hanatani Shinsuke
    Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University
  • Onoue Yoshiro
    Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University
  • Ishida Toshifumi
    Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University
  • Arima Yuichiro
    Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University
  • Nakamura Taishi
    Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University
  • Yamamoto Eiichiro
    Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University
  • Senokuchi Takafumi
    Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University
  • Yoshizawa Tatsuya
    Department of Medical Biochemistry, Faculty of Life Sciences, Kumamoto University
  • Sata Masataka
    Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School
  • Kim-Mitsuyama Shokei
    Departments of Pharmacology and Molecular Therapeutics, Faculty of Life Sciences, Kumamoto University
  • Nakagata Naomi
    Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University
  • Bober Eva
    Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research
  • Braun Thomas
    Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research
  • Kaikita Koichi
    Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University
  • Yamagata Kazuya
    Department of Medical Biochemistry, Faculty of Life Sciences, Kumamoto University
  • Tsujita Kenichi
    Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University

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Other Title
  • Sirtuin-7 as a Novel Therapeutic Target in Vascular Smooth Muscle Cell Proliferation and Remodeling

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<p>Background:Sirt7 is a recently identified sirtuin and has important roles in various pathological conditions, including cancer progression and metabolic disorders. It has previously been reported that Sirt7 is a key molecule in acute myocardial wound healing and pressure overload-induced cardiac hypertrophy. In this study, the role of Sirt7 in neointimal formation after vascular injury is investigated.</p><p>Methods and Results:Systemic (Sirt7−/−) and smooth muscle cell-specific Sirt7-deficient mice were subjected to femoral artery wire injury. Primary vascular smooth muscle cells (VSMCs) were isolated from the aorta of wild type (WT) and Sirt7−/−mice and their capacity for cell proliferation and migration was compared. Sirt7 expression was increased in vascular tissue at the sites of injury. Sirt7−/−mice demonstrated significant reduction in neointimal formation compared to WT mice. In vitro, Sirt7 deficiency attenuated the proliferation of serum-induced VSMCs. Serum stimulation-induced upregulation of cyclins and cyclin-dependent-kinase 2 (CDK2) was significantly attenuated in VSMCs of Sirt7−/−compared with WT mice. These changes were accompanied by enhanced expression of the microRNA 290-295 cluster, the translational negative regulator of CDK2, in VSMCs of Sirt7−/−mice. It was confirmed that smooth muscle cell-specific Sirt7-deficient mice showed significant reduction in neointima compared with control mice.</p><p>Conclusions:Sirt7 deficiency attenuates neointimal formation after vascular injury. Given the predominant role in vascular neointimal formation, Sirt7 is a potentially suitable target for treatment of vascular diseases.</p>

Journal

  • Circulation Journal

    Circulation Journal 85 (12), 2232-2240, 2021-11-25

    The Japanese Circulation Society

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