title: Oscillatory shear stress, flow-mediated dilatation, and circulating microparticles at sea level and high altitude.
abstract: Exposing the endothelium to acute periods of imposed oscillatory shear stress reduces endothelial function and elevates circulating microparticles (MPs). Oscillatory shear stress may be especially pathogenic when superimposed on hypoxia, an environmental stimulus that disrupts the endothelial milieu. We examined the effects of acute manipulation of oscillatory shear stress on endothelial function and circulating MPs at sea level (SL) and high altitude (HA).
  
  
  
  Healthy adults (n = 12) participated, once at SL and once on the second or third day at HA (3800 m). Oscillatory shear stress was provoked using a 30-min distal cuff occlusion intervention (75 mmHg). Endothelial function was assessed before and immediately after the intervention in the brachial artery by reactive hyperaemia flow-mediated dilatation (FMD). Venous blood samples of MPs (flow cytometry) were obtained before and during the last five minutes of the shear intervention.
  
  
  
  At baseline, circulating MPs were two-fold higher at HA (p = 0.011) and brachial artery diameter was constricted (p = 0.015). Although the intervention at SL increased endothelial-derived MPs by 83 ± 39% (mean ± SEM; p = 0.021), FMD was unaltered. Conversely, at HA, the intervention elicited a 26 ± 11% reduction in FMD (p = 0.020); this reduction was inversely correlated with the change in total circulating MPs (r = -0.737, p = 0.006) and the change in endothelial-derived MPs (r = -0.614, p = 0.034).
  
  
  
  The vascular endothelium appears to be susceptible to periods of oscillatory shear stress at HA, where impairments in endothelium-dependent vasodilatation may be amplified by endothelial injury. These findings have important implications for understanding the early impact of clinical situations of hypoxaemia on the vascular endothelium.
authors.affiliation: Centre for Heart, Lung, and Vascular Health School of Health and Exercise Science, University of British Columbia, Kelowna, Canada. Electronic address: 15jct1@queensu.ca.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Tremblay
authors.affiliation: Department of Emergency Medicine, University of Maryland, Baltimore, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Thom
authors.affiliation: Department of Emergency Medicine, University of Maryland, Baltimore, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: Centre for Heart, Lung, and Vascular Health School of Health and Exercise Science, University of British Columbia, Kelowna, Canada.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Ainslie
mesh_terms: D000328:Adult; D000531:Altitude; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D039421:Integrin alpha2 / Q000097:blood; D008297:Male; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood; D012039:Regional Blood Flow; D013314:Stress, Mechanical; D013997:Time Factors; D018608:Ultrasonography, Doppler; D014664:Vasodilation; D055815:Young Adult
chemical_list: D015415:Biomarkers; C056564:ITGA2B protein, human; D039421:Integrin alpha2; D019408:Platelet Endothelial Cell Adhesion Molecule-1
keywords: Cell-derived microparticles; Endothelium; Haemodynamics; Hypoxia; Vascular; Vasodilatation