Sirt7 Deficiency Attenuates Neointimal Formation Following Vascular Injury by Modulating Vascular Smooth Muscle Cell Proliferation
Sirt7 Deficiency Attenuates Neointimal Formation Following Vascular Injury by Modulating Vascular Smooth Muscle Cell Proliferation
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DOI：
10.1253/circj.cj-20-0936
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发表时间：
2021-12-01
影响因子：
3.3
通讯作者：
Tsujita, Kenichi
中科院分区：
文献类型：
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作者：
Kimura, Yuichi;Izumiya, Yasuhiro;Tsujita, Kenichi
背景资料：Sirt 7是最近鉴定的sirtuin，并且在各种病理状况中具有重要作用，包括癌症进展和代谢紊乱。先前已报道Sirt 7是急性心肌创伤愈合和压力超负荷诱导的心脏肥大中的关键分子。在这项研究中，Sirt 7在血管损伤后新生内膜形成的作用investigated.Methods和结果：全身（Sirt 7（-/-））和平滑肌细胞特异性Sirt 7缺陷小鼠进行股动脉线损伤。从野生型（WT）和Sirt 7（-/-）小鼠的主动脉分离原代血管平滑肌细胞（VSMC），并比较它们的细胞增殖和迁移能力。Sirt 7表达在损伤部位的血管组织中增加。与WT小鼠相比，Sirt 7（-/-）小鼠的新生内膜形成显著减少。在体外，Sirt 7缺陷减弱血清诱导的VSMCs的增殖。与WT小鼠相比，血清刺激诱导的Sirt 7（-/-）VSMCs中细胞周期蛋白和细胞周期蛋白依赖性激酶2（CDK 2）的上调显著减弱。这些变化伴随着Sirt 7（-/-）小鼠VSMC中microRNA 290-295簇（CDK 2的翻译负调控因子）的表达增强。结果证实，平滑肌细胞特异性Sirt 7缺陷小鼠表现出显着减少新生内膜与对照mice.Conclusions相比：Sirt 7缺陷减弱血管损伤后新生内膜形成。鉴于在血管新生内膜形成中的主要作用，Sirt 7是用于治疗血管疾病的潜在合适靶点。
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.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.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.