Vimentin knockout results in increased expression of sub-endothelial basement membrane components and carotid stiffness in mice

• Published in: Scientific reports Vol. 7; no. 1; pp. 11628 - 15
• Main Authors: Langlois, Benoit, Belozertseva, Ekaterina, Parlakian, Ara, Bourhim, Mustapha, Gao-Li, Jacqueline, Blanc, Jocelyne, Tian, Lei, Coletti, Dario, Labat, Carlos, Ramdame-Cherif, Zhor, Challande, Pascal, Regnault, Véronique, Lacolley, Patrick, Li, Zhenlin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.09.2017; Nature Publishing Group
• Subjects: 631/443/592/75/593/2724; 631/80/128/1580; Actin; Actomyosin; Animals; Basement Membrane - metabolism; Basement membranes; Biochemistry, Molecular Biology; Biomarkers; Blood Pressure; Cadherins; Carotid Artery Diseases - etiology; Carotid Artery Diseases - metabolism; Carotid Artery Diseases - physiopathology; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Collagen (type IV); Disease Models, Animal; Elastin; Electron microscopy; Endothelial cells; Endothelium - metabolism; Extracellular signal-regulated kinase; Fibronectin; Filaments; Fluorescent Antibody Technique; Gene Expression Regulation; Humanities and Social Sciences; Intermediate filaments; Intermediate Filaments - genetics; Intermediate Filaments - metabolism; Laminin; Life Sciences; Mechanical Phenomena; Mechanical properties; Membranes; Mice; Mice, Knockout; Microscopy, Confocal; multidisciplinary; Muscle contraction; Myosin; Perlecan; Rodents; Science; Science (multidisciplinary); Smooth muscle; Talin; Vascular Stiffness - genetics; Vasodilation - genetics; Vimentin; Vimentin - deficiency; Vinculin; Von Willebrand factor
• ISSN: 2045-2322; 2045-2322
• 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 v , 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.