Understanding how matrix rigidity and cytoskeletal crosstalk regulate vascular smooth muscle cell ageing
了解基质刚性和细胞骨架串扰如何调节血管平滑肌细胞衰老
基本信息
- 批准号:2868506
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:英国
- 项目类别:Studentship
- 财政年份:2023
- 资助国家:英国
- 起止时间:2023 至 无数据
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Maintaining aortic compliance, the ability of the aorta to change shape in response to changes in blood pressure, is essential for healthy ageing. The aortic wall is comprised of elastic and non-elastic components. As we age, the elastic components become degraded, increasing the stiffness and reducing aortic compliance. This is a major risk-factor for numerous age-related diseases.Vascular Smooth Muscle Cells (VSMCs) are the predominant cell type of the aortic wall. These mechanosensitive cells sense increased aortic wall stiffness and generate enhanced actomyosin-driven contractile forces. This prevents the deformation of the aortic wall and further reduces aortic compliance. However, mechanisms regulating VSMC force generation in response to increased aortic wall stiffness remain unknown. This studentship seeks to address this gap in our knowledge and identify novel pathways regulating this process.Recently we have shown that VSMCs grown on rigid surfaces display decreased microtubule stability. We hypothesise that microtubule disassembly activates a RhoA/GEF-H1 signalling pathway, which in turn promotes actin polymerisation and enhances actomyosin-derived force production. This project seeks to determine if: (1) microtubule destabilisation promotes enhanced actomyosin force production; (2) targeting RhoA/GEF-H1 is sufficient to alleviate enhanced actomyosin force generation; and (3) RhoA alters cell-matrix adhesion signalling pathways in response to matrix stiffness.
保持主动脉顺应性,即主动脉响应血压变化而改变形状的能力,对于健康的衰老至关重要。主动脉壁由弹性和非弹性组件组成。随着年龄的增长,弹性组件会退化,增加刚度并降低主动脉顺应性。血管平滑肌细胞(VSMC)是主动脉壁的主要细胞类型。这些机械敏感细胞感觉到主动脉壁硬度的增加,并产生增强的肌动球蛋白驱动的收缩力。这防止了主动脉壁的变形并进一步降低了主动脉顺应性。然而,调节VSMC力产生的机制,以响应增加主动脉壁刚度仍然未知。本研究旨在填补这一知识空白,并确定调控这一过程的新途径。最近,我们发现在刚性表面上生长的VSMCs显示微管稳定性降低。我们假设微管分解激活RhoA/GEF-H1信号通路,这反过来又促进肌动蛋白聚合,增强肌动球蛋白衍生的力的产生。该项目旨在确定:(1)微管不稳定是否促进增强的肌动球蛋白力产生;(2)靶向RhoA/GEF-H1足以减轻增强的肌动球蛋白力产生;(3)RhoA改变细胞-基质粘附信号通路以响应基质硬度。
项目成果
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其他文献
吉治仁志 他: "トランスジェニックマウスによるTIMP-1の線維化促進機序"最新医学. 55. 1781-1787 (2000)
Hitoshi Yoshiji 等:“转基因小鼠中 TIMP-1 的促纤维化机制”现代医学 55. 1781-1787 (2000)。
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LiDAR Implementations for Autonomous Vehicle Applications
- DOI:
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2021 - 期刊:
- 影响因子:0
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吉治仁志 他: "イラスト医学&サイエンスシリーズ血管の分子医学"羊土社(渋谷正史編). 125 (2000)
Hitoshi Yoshiji 等人:“血管医学与科学系列分子医学图解”Yodosha(涉谷正志编辑)125(2000)。
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Effect of manidipine hydrochloride,a calcium antagonist,on isoproterenol-induced left ventricular hypertrophy: "Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,K.,Teragaki,M.,Iwao,H.and Yoshikawa,J." Jpn Circ J. 62(1). 47-52 (1998)
钙拮抗剂盐酸马尼地平对异丙肾上腺素引起的左心室肥厚的影响:“Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,
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An implantable biosensor microsystem for real-time measurement of circulating biomarkers
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2908918 - 财政年份:2027
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2908693 - 财政年份:2027
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2908917 - 财政年份:2027
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2876993 - 财政年份:2027
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