著作: Kimura Yuichi/Izumiya Yasuhiro/Araki Satoshi/Yamamura Satoru/Hanatani Shinsuke/Onoue Yoshiro/Ishida Toshifumi/Arima Yuichiro/Nakamura Taishi/Yamamoto Eiichiro/Senokuchi Takafumi/Yoshizawa Tatsuya/[佐田 政隆]/Kim-Mitsuyama Shokei/Nakagata Naomi/Bober Eva/Braun Thomas/Kaikita Koichi/Yamagata Kazuya/Tsujita Kenichi/Sirt7 Deficiency Attenuates Neointimal Formation Following Vascular Injury by Modulating Vascular Smooth Muscle Cell Proliferation/[Circulation Journal]
(英) Sirt7 Deficiency Attenuates Neointimal Formation Following Vascular Injury by Modulating Vascular Smooth Muscle Cell Proliferation
(英) 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.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 Sirt7mice and their capacity for cell proliferation and migration was compared. Sirt7 expression was increased in vascular tissue at the sites of injury. Sirt7mice 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 Sirt7compared 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 Sirt7mice. It was confirmed that smooth muscle cell-specific Sirt7-deficient mice showed significant reduction in neointima compared with control mice. 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.
Circulation Journal([社団法人 日本循環器学会])
(pISSN: 1346-9843, eISSN: 1347-4820)
|年月日||必須||2021年 11月 25日|