title: Reduced cyclic stretch, endothelial dysfunction, and oxidative stress: an ex vivo model.
abstract: BACKGROUND
  The objective of this study was to investigate whether reduction of cyclic circumferential stretch will impair endothelial function and elevate basal levels of oxidative stress, both known risk factors linked to cardiovascular disease.
  
  
  METHODS
  Ex vivo and in vitro models were used to perfuse porcine carotid arteries and porcine endothelial cells, respectively, for 24 h. In both cases, one group was allowed to stretch naturally when exposed to a pulse shear stress (6+/-3 dynes/cm(2)) combined with a pulse pressure of 80+/-10 mmHg, yielding a physiological cyclic stretch of 4-5%. This group was compared to a reduced stretch group, achieved by wrapping the arterial segment with a silicon band or by seeding the endothelial cells inside less compliant tubes, decreasing cyclic stretch to 1%.
  
  
  RESULTS
  The experimentally reduced compliance caused a significant decrease in bradykinin-dependent vascular relaxation. Reduced compliance significantly decreased the phosphorylation of serine 1177 (Ser1177) on eNOS, suggesting the activity of eNOS was decreased. Overall production of reactive oxygen species was increased by reducing compliance, as visualized with DHE. Finally, p22-phox and p47-phox, key players in the superoxide-generating NAD(P)H oxidase, were also up-regulated by reduced compliance.
  
  
  CONCLUSIONS
  These findings point out how reduced arterial compliance increases the risk of arterial disease by creating a less functional endothelium, interrupting the eNOS activation pathway, and increasing the vascular levels of oxidative stress.
authors.affiliation: LHTC, Institute of Bioengineering, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland. tyler.thacher@epfl.ch
authors.forename: Tyler
authors.initials: T
authors.lastname: Thacher
authors.forename: Veronica
authors.initials: V
authors.lastname: Gambillara
authors.forename: Rafaela F
authors.initials: RF
authors.lastname: da Silva
authors.forename: Paolo
authors.initials: P
authors.lastname: Silacci
authors.forename: Nikos
authors.initials: N
authors.lastname: Stergiopulos
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001920:Bradykinin / Q000187:drug effects; D002343:Carotid Artery, Internal / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003187:Compliance / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology*; D023421:Models, Animal; D019255:NADPH Oxidases / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D011673:Pulsatile Flow; D017382:Reactive Oxygen Species / Q000378:metabolism; D033081:Shear Strength / Q000187:drug effects / Q000502:physiology; D013314:Stress, Mechanical; D013552:Swine; D013718:Tensile Strength / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; C086986:CYBA protein, human; C060505:neutrophil cytosolic factor 1; D001920:Bradykinin