Inserm, UMR_S 1116, Université de Lorraine, Nancy, France.
Sorbonne Universités, UPMC Univ Paris 06, INSERM ERL U1164, Institut Biologie Paris-Seine, Paris, CNRS, UMR 8256, France.
Sci Rep. 2017 Sep 14;7(1):11628. doi: 10.1038/s41598-017-12024-z.
Intermediate filaments are involved in stress-related cell mechanical properties and in plasticity via the regulation of focal adhesions (FAs) and the actomyosin network. We investigated whether vimentin regulates endothelial cells (ECs) and vascular smooth muscle cells (SMCs) and thereby influences vasomotor tone and arterial stiffness. Vimentin knockout mice (Vim) exhibited increased expression of laminin, fibronectin, perlecan, collagen IV and VE-cadherin as well as von Willebrand factor deposition in the subendothelial basement membrane. Smooth muscle (SM) myosin heavy chain, α-SM actin and smoothelin were decreased in Vim mice. Electron microscopy revealed a denser endothelial basement membrane and increased SM cell-matrix interactions. Integrin α, talin and vinculin present in FAs were increased in Vim mice. Phosphorylated FA kinase and its targets Src and ERK1/2 were elevated in Vim mice. Knockout of vimentin, but not of synemin, resulted in increased carotid stiffness and contractility and endothelial dysfunction, independently of blood pressure and the collagen/elastin ratio. The increase in arterial stiffness in Vim mice likely involves vasomotor tone and endothelial basement membrane organization changes. At the tissue level, the results show the implication of FAs both in ECs and vascular SMCs in the role of vimentin in arterial stiffening.
中间丝参与与应激相关的细胞力学特性和通过调节黏着斑（FAs）和肌动球蛋白网络的可塑性。我们研究了中间丝是否调节内皮细胞（ECs）和血管平滑肌细胞（SMCs），从而影响血管舒缩功能和动脉僵硬。波形蛋白敲除小鼠（Vim）表现出层粘连蛋白、纤维连接蛋白、perlecan、胶原 IV 和 VE-钙粘蛋白的表达增加，以及血管内皮下基底膜中 von Willebrand 因子的沉积。Vim 小鼠中的平滑肌（SM）肌球蛋白重链、α-SM 肌动蛋白和 smoothelin 减少。电子显微镜显示出更密集的内皮基底膜和增加的 SM 细胞-基质相互作用。黏着斑中的整合素α、talin 和 vinculin 在 Vim 小鼠中增加。黏着斑激酶及其靶标 Src 和 ERK1/2 的磷酸化在 Vim 小鼠中升高。波形蛋白的敲除，而不是 synemin 的敲除，导致颈动脉僵硬和收缩性增加以及内皮功能障碍，独立于血压和胶原/弹性蛋白比例。Vim 小鼠中动脉僵硬的增加可能涉及血管舒缩功能和内皮基底膜组织变化。在组织水平上，结果表明黏着斑在 ECs 和血管平滑肌细胞中均涉及到波形蛋白在动脉僵硬中的作用。
