title: Mechanoresponsive networks controlling vascular inflammation.
abstract: Atherosclerosis is a chronic inflammatory disease of arteries that develops preferentially at branches and bends that are exposed to disturbed blood flow. Vascular function is modified by flow, in part, via the generation of mechanical forces that alter multiple physiological processes in endothelial cells. Shear stress has profound effects on vascular inflammation; high uniform shear stress prevents leukocyte recruitment to the vascular wall by reducing endothelial expression of adhesion molecules and other inflammatory proteins, whereas low oscillatory shear stress has the opposite effects. Here, we review the molecular mechanisms that underpin the effects of shear stress on endothelial inflammatory responses. They include shear stress regulation of inflammatory mitogen-activated protein kinase and nuclear factor-κB signaling. High shear suppresses these pathways through the induction of several negative regulators of inflammation, whereas low shear promotes inflammatory signaling. Furthermore, we summarize recent studies indicating that inflammatory signaling is highly sensitive to pulse wave frequencies, magnitude, and direction of flow. Finally, the importance of systems biology approaches (including omics studies and functional screening) to identify novel mechanosensitive pathways is discussed.
authors.affiliation: From the Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Bryan
authors.affiliation: From the Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Hayley
authors.initials: H
authors.lastname: Duckles
authors.affiliation: From the Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Shuang
authors.initials: S
authors.lastname: Feng
authors.affiliation: From the Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Sarah T
authors.initials: ST
authors.lastname: Hsiao
authors.affiliation: From the Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Hyejeong R
authors.initials: HR
authors.lastname: Kim
authors.affiliation: From the Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Jovana
authors.initials: J
authors.lastname: Serbanovic-Canic
authors.affiliation: From the Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Evans
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005786:Gene Expression Regulation; D006439:Hemodynamics; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D012039:Regional Blood Flow; D013314:Stress, Mechanical
chemical_list: D018836:Inflammation Mediators
keywords: endothelium; inflammation; shear stress