title: Oscillatory shear stress and reduced compliance impair vascular functions.
abstract: Shear stress has been shown to influence endothelial cell gene expression and morphology. In particular, low and bi-directional shear stress, mimicking conditions at plaque-prone areas, down-regulates the expression of several atheroprotective genes, and up-regulates that of other genes considered as pro-inflammatory. Another mechanical situation thought to have a negative influence on vascular functions is arterial stiffness. Loss of arterial compliance occurs during ageing, in diabetic as well as in hypertensive patients. In this work we investigated the effects of these two particular hemodynamic environments (bi-directional shear stress and reduced compliance), using a recently developed perfusion system allowing to expose native arteries in vitro to complex hemodynamic environments. We were able to show that both plaque-prone shear stress and reduced compliance trigger endothelial dysfunction, but via different mechanisms. Only reduced compliance affected vascular contractility, inducing a dedifferentiation of smooth muscle cells and a consequent loss of norepinephrine sensitivity.
authors.affiliation: Laboratory of Hemodynamics and Cardiovascular Technology, Swiss Federal Institute of Technology, Lausanne, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Thacher
authors.forename: V
authors.initials: V
authors.lastname: Gambillara
authors.forename: R
authors.initials: R
authors.lastname: Da Silva
authors.forename: G
authors.initials: G
authors.lastname: Montorzi
authors.forename: N
authors.initials: N
authors.lastname: Stergiopulos
authors.forename: P
authors.initials: P
authors.lastname: Silacci
mesh_terms: D002454:Cell Differentiation; D004548:Elasticity; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D009638:Norepinephrine; D010477:Perfusion; D011673:Pulsatile Flow; D013314:Stress, Mechanical; D014661:Vasoconstriction; D014664:Vasodilation
chemical_list: D052250:Nitric Oxide Synthase Type III; D009638:Norepinephrine