title: Haemodynamics Regulate Fibronectin Assembly via PECAM.
abstract: Fibronectin (FN) assembly and fibrillogenesis are critically important in both development and the adult organism, but their importance in vascular functions is not fully understood. Here we identify a novel pathway by which haemodynamic forces regulate FN assembly and fibrillogenesis during vascular remodelling. Induction of disturbed shear stress in vivo and in vitro resulted in complex FN fibril assembly that was dependent on the mechanosensor PECAM. Loss of PECAM also inhibited the cell-intrinsic ability to remodel FN. Gain- and loss-of-function experiments revealed that PECAM-dependent RhoA activation is required for FN assembly. Furthermore, PECAM-/-mice exhibited reduced levels of active β1 integrin that were responsible for reduced RhoA activation and downstream FN assembly. These data identify a new pathway by which endothelial mechanotransduction regulates FN assembly and flow-mediated vascular remodelling.
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Givens
authors.affiliation: Wellcome Trust Center for Human Genetics, Oxford OX3 7BN, UK.
authors.forename: John S
authors.initials: JS
authors.lastname: Reader
authors.affiliation: Wellcome Trust Center for Human Genetics, Oxford OX3 7BN, UK.
authors.forename: Ellie
authors.initials: E
authors.lastname: Tzima
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D005353:Fibronectins / Q000378:metabolism*; D006439:Hemodynamics; D019012:Integrin beta1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D066253:Vascular Remodeling; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D005353:Fibronectins; D019012:Integrin beta1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D020742:rhoA GTP-Binding Protein