Abstract
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 αv, 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.
Highlights
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
To examine the expression of Vim in arteries, we stained the carotid artery of adult mice with antibodies against α-smooth muscle actin (SMA) in SMCs and to CD31 in ECs. Both α-SMA-positive and CD31-positive cells stained for Vim indicating that Vim was present in SMCs and ECs (Fig. 1A,B)
Summary
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. The increase in arterial stiffness in Vim−/− mice likely involves vasomotor tone and endothelial basement membrane organization changes. The results show the implication of FAs both in ECs and vascular SMCs in the role of vimentin in arterial stiffening. Contrasting reports show that Vim decreases FA size on the one hand[5,34] and increases cell stiffness on the other[35,36] which raises the hypothesis that Vim and/or Synm exert a complex regulating action on SMC and EC functions and are involved in arterial stiffening. We have identified a targeted approach to treat arterial stiffening
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