Vimentin regulates Notch signaling strength and arterial remodeling in response to hemodynamic stress

Nicole C.A. van Engeland, Freddy Suarez Rodriguez, Adolfo Rivero-Müller, Tommaso Ristori, Camille L. Duran, Oscar M.J.A. Stassen, Daniel Antfolk, Rob C.H. Driessen, Saku Ruohonen, Suvi T. Ruohonen, Salla Nuutinen, Eriika Savontaus, Sandra Loerakker, Kayla J. Bayless, Marika Sjöqvist, Carlijn V.C. Bouten, John E. Eriksson, Cecilia M. Sahlgren (Corresponding author)

Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

11 Citaten (Scopus)
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Samenvatting

The intermediate filament (IF) cytoskeleton has been proposed to regulate morphogenic processes by integrating the cell fate signaling machinery with mechanical cues. Signaling between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) through the Notch pathway regulates arterial remodeling in response to changes in blood flow. Here we show that the IF-protein vimentin regulates Notch signaling strength and arterial remodeling in response to hemodynamic forces. Vimentin is important for Notch transactivation by ECs and vimentin knockout mice (VimKO) display disrupted VSMC differentiation and adverse remodeling in aortic explants and in vivo. Shear stress increases Jagged1 levels and Notch activation in a vimentin-dependent manner. Shear stress induces phosphorylation of vimentin at serine 38 and phosphorylated vimentin interacts with Jagged1 and increases Notch activation potential. Reduced Jagged1-Notch transactivation strength disrupts lateral signal induction through the arterial wall leading to adverse remodeling. Taken together we demonstrate that vimentin forms a central part of a mechanochemical transduction pathway that regulates multilayer communication and structural homeostasis of the arterial wall.

Originele taal-2Engels
Artikelnummer12415
Aantal pagina's14
TijdschriftScientific Reports
Volume9
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 27 aug 2019

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