Microskeletal stiffness promotes aortic aneurysm by sustaining pathological vascular smooth muscle cell mechanosensation via Piezo1.
Microskeletal stiffness promotes aortic aneurysm by sustaining pathological vascular smooth muscle cell mechanosensation via Piezo1.
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微骨骼刚度通过Piezo1维持病理性血管平滑肌细胞机械感觉促进主动脉瘤。
DOI：
10.1038/s41467-021-27874-5
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发表时间：
2022-01-26
影响因子：
16.6
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Qian W;Hadi T;Silvestro M;Ma X;Rivera CF;Bajpai A;Li R;Zhang Z;Qu H;Tellaoui RS;Corsica A;Zias AL;Garg K;Maldonado T;Ramkhelawon B;Chen W
血管壁的机械过载是危及生命的腹主动脉瘤（AAA）的病理标志。然而，这种机械应力如何在血管平滑肌细胞（VSMC）的单细胞水平上产生共振尚不清楚。在这里，我们显示有缺陷的机械表型签名的VSMC在AAA测量超声镊子为基础的微机械系统和单细胞RNA测序技术。理论模型预测，细胞骨架改变燃料电池的VSMC膜的张力，从而调节其mechanoallostatic响应，这是通过现场微观力学测量验证。在机械上，VSMC通过在AAA促进信号Netrin-1的存在下上调细胞骨架交联剂α-actinin 2逐渐采取机械固体样状态，从而直接为机械感觉离子通道Piezo 1的活性提供动力。抑制Piezo 1可通过减轻病理性血管重塑防止小鼠发生AAA。我们的研究结果表明，VSMC的机械感觉行为的偏差是不利的AAA和确定Piezo 1作为一个新的罪魁祸首的机械疲劳主动脉在AAA。据报道，机械生物学信号有助于腹主动脉瘤（AAA）的发展。在这里，作者报告说，微骨骼刚度和Piezo 1介导的机制影响血管平滑肌细胞机械感觉和AAA疾病的发展。
Mechanical overload of the vascular wall is a pathological hallmark of life-threatening abdominal aortic aneurysms (AAA). However, how this mechanical stress resonates at the unicellular level of vascular smooth muscle cells (VSMC) is undefined. Here we show defective mechano-phenotype signatures of VSMC in AAA measured with ultrasound tweezers-based micromechanical system and single-cell RNA sequencing technique. Theoretical modelling predicts that cytoskeleton alterations fuel cell membrane tension of VSMC, thereby modulating their mechanoallostatic responses which are validated by live micromechanical measurements. Mechanistically, VSMC gradually adopt a mechanically solid-like state by upregulating cytoskeleton crosslinker, α-actinin2, in the presence of AAA-promoting signal, Netrin-1, thereby directly powering the activity of mechanosensory ion channel Piezo1. Inhibition of Piezo1 prevents mice from developing AAA by alleviating pathological vascular remodeling. Our findings demonstrate that deviations of mechanosensation behaviors of VSMC is detrimental for AAA and identifies Piezo1 as a novel culprit of mechanically fatigued aorta in AAA. Mechanobiological signals have been reported to contribute to abdominal aortic aneurysm (AAA) development. Here the authors report that the microskeletal stiffness and a Piezo1-mediated mechanism influence vascular smooth muscle cell mechanosensation and AAA disease development.
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影响因子：
4.6
作者：
Cohen, Ohad;Safran, Samuel A.
通讯作者：
Safran, Samuel A.
影响因子：
16.6
作者：
Cox CD;Bae C;Ziegler L;Hartley S;Nikolova-Krstevski V;Rohde PR;Ng CA;Sachs F;Gottlieb PA;Martinac B
通讯作者：
Martinac B
影响因子：
3.4
作者：
Francis, Madison L.;Ricketts, Shea N.;Robertson-Anderson, Rae M.
通讯作者：
Robertson-Anderson, Rae M.
影响因子：
4.3
作者：
Fillinger, MF;Marra, SP;Kennedy, FE
通讯作者：
Kennedy, FE
由机械敏感离子通道 PIEZO1 和组织力学介导的前馈机制促进胶质瘤侵袭。
影响因子：
16.2
作者：
Chen, Xin;Wanggou, Siyi;Huang, Xi
通讯作者：
Huang, Xi