Pivotal role of longevity gene Sir2 on molecula r mechanisms of vascular calcification via cellular senescence

长寿基因Sir2在细胞衰老血管钙化分子机制中的关键作用

• 批准号: 21590947
• 负责人: IIJIMA Katsuya
• 金额: $ 2.91万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590947/
• 关键词: 血管石灰化; 細胞老化; 長寿遺伝子Sirtuin; 動脈硬化; 長寿遺伝子

Vascular aging manifest several features, namely atherosis, sclerosis and calcified change. Vascular calcification makes the management of hemodynamics more difficult in the elderly, because the stiffened vasculatures with ectopic calcification contribute to excessive blood pressure variability, isolated systolic hypertension with increased arterial wave reflectance, and subsequent ischemic cerebro-/cardio-vascular(CV) events. Vascular calcification has been previously shown to result from passive precipitation of calcium with aging and osteoporosis. However, accumulating recent evidences have shown it to be attributable to an active' cell-mediated process' resembling osteogenesis in bone rather than passive mineral precipitation in vascular smooth muscle cells(SMC). Cellular senescence has been recently shown to be linked to atherosclerogenesis ; however, few reports have addressed whether cellular senescence is associated with SMC calcification. Our new findings show that the senescent phenotypic change is associated with osteoblastic trans-differentiation in SMC and mammalian sirtuin SIRT1, which is well known as a longevity gene, can exert a protective effect on the cellular senescence-related vascular calcification under hyperphosphatemia. In addition, the activation of Runx2, a potent osteogenic transcriptional factor, in SMC is regulated by SIRT1-p21 axis. The identification of therapeutic targets which can slow down the progression or even reverse the senescent phenotypic change in SMC could be an important step forward in the treatment of vascular calcification.

血管衰老表现为动脉粥样硬化、硬化和钙化改变。血管钙化使老年人的血流动力学管理更加困难，因为异位钙化的硬化血管导致血压变异性过高，单纯的收缩期高血压伴动脉波反射增加，以及随后的脑/心血管(CV)事件。血管钙化以前被证明是由于衰老和骨质疏松导致的被动钙沉淀。然而，最近积累的证据表明，它可归因于一种类似于骨中成骨的主动“细胞介导过程”，而不是血管平滑肌细胞(SMC)中被动的矿物质沉积。细胞衰老最近被证明与动脉粥样硬化形成有关，然而，很少有报道指出细胞衰老是否与SMC钙化有关。我们的新发现表明，SMC的衰老表型改变与成骨细胞的转分化有关，哺乳动物sirtuin SIRT1是一个众所周知的长寿基因，它对高磷血症下细胞衰老相关的血管钙化具有保护作用。此外，SMC中的成骨转录因子Runx2的激活受SIRT1-p21轴的调控。寻找能够延缓甚至逆转SMC衰老表型改变的治疗靶点，可能是血管钙化治疗的重要一步。

项目成果

Sirt1は細胞老化抑制を介して血管平滑筋細胞石灰化に対する保護作用を発揮する.

Sirt1 通过抑制细胞衰老发挥针对血管平滑肌细胞钙化的保护作用。

• 发表时间: 2009
• 作者: 竹村彩;飯島勝矢;他7名
• 通讯作者: 他7名

長寿因子SIRT1による血管石灰化の抑制

长寿因子 SIRT1 抑制血管钙化

• 发表时间: 2011
• 作者: Tatsuya Morimoto;Masatoshi Fujita;Yoichi Sunagawa;Hiromichi Wada;Tomohide Takaya;Shigeki Yanagi;Akira Marui;Tadashi Ikeda;Akira ShimatsuKoji Hasegawa;飯島勝矢
• 通讯作者: 飯島勝矢

Inhibition of Apoptosis-Based Vascular Smooth Muscle Cell Calcification by Cilostazol is Associated with Restoration of Mammalian Sirtuin SIRT1

西洛他唑对基于凋亡的血管平滑肌细胞钙化的抑制与哺乳动物 Sirtuin SIRT1 的恢复相关

• 发表时间: 2011
• 作者: Katsuya Iijima;Go Hashizume;Bo-Kyung Son;Hidetaka Ota;Sumito Ogawa;Masato Eto;Masahiro Akishita;Yasuyoshi Ouchi.
• 通讯作者: Yasuyoshi Ouchi.

Clinical features and molecular mechanisms of vascular aging : Impact of vascular calcification

血管老化的临床特征和分子机制：血管钙化的影响

• 发表时间: 2011
• 作者: Otake A;Takeishi Y;et al;飯島勝矢
• 通讯作者: 飯島勝矢

災害時における高齢者医療対策-避難所生活から高齢者をどう守るか-循環器系疾患の対策とストレスによる誘引

灾害时老年人的医疗对策 - 如何保护居住在避难所的老年人 - 循环系统疾病及压力诱发因素的对策

• 发表时间: 2011
• 作者: 一色政志;ほか;Harata K;飯島勝矢
• 通讯作者: 飯島勝矢