title: Altered Profile of Circulating Endothelial-Derived Microparticles in Ventilator-Induced Lung Injury.
abstract: OBJECTIVE
  Pulmonary endothelial cell injury is central to the pathophysiology of acute lung injury. Mechanical ventilation can cause endothelial disruption and injury, even in the absence of preexisting inflammation. Platelet-endothelial cell adhesion molecule-1 is a transmembrane protein connecting adjacent endothelial cells. We hypothesized that injurious mechanical ventilation will increase circulating lung endothelial-derived microparticles, defined as microparticles positive for platelet-endothelial cell adhesion molecule-1, which could serve as potential biomarkers and mediators of ventilator-induced lung injury.
  
  
  METHODS
  Prospective randomized, controlled, animal investigation.
  
  
  METHODS
  A hospital preclinical animal laboratory.
  
  
  METHODS
  Forty-eight Sprague-Dawley rats.
  
  
  METHODS
  Animals were randomly allocated to one of the three following ventilatory protocols for 4 hours: spontaneous breathing (control group), mechanical ventilation with low tidal volume (6 mL/kg), and mechanical ventilation with high tidal volume (20 mL/kg). In both mechanical ventilation groups, positive end-expiratory pressure of 2 cm H2O was applied.
  
  
  RESULTS
  We analyzed histologic lung damage, gas exchange, wet-to-dry lung weight ratio, serum cytokines levels, circulating endothelial-derived microparticles, platelet-endothelial cell adhesion molecule-1 lung protein content, and immunohistochemistry. When compared with low-tidal volume mechanical ventilation, high-tidal volume ventilation increased lung edema score and caused gas-exchange deterioration. These changes were associated with a marked increased of circulating endothelial-derived microparticles and a reduction of platelet-endothelial cell adhesion molecule-1 protein levels in the high-tidal volume lungs (p < 0.0001).
  
  
  CONCLUSIONS
  There is an endothelial-derived microparticle profile associated with disease-specific features of ventilator-induced lung injury. This profile could serve both as a biomarker of acute lung injury and, potentially, as a mediator of systemic propagation of pulmonary inflammatory response.
authors: 1CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain. 2Multidisciplinary Organ Dysfunction Evaluation Research Network, Research Unit, Hospital Universitario Dr. Negrin, Las Palmas de Gran Canaria, Spain. 3Department of Anatomy, Pathology and Histology, University of La Laguna, Tenerife, Spain. 4Department of Immunology, Hospital Universitario Dr. Negrin, Las Palmas de Gran Canaria, Spain. 5Department of Immunology, Hospital San Espases, Palma de Mallorca, Spain. 6Department of Clinical Biochemistry, Hospital Universitario NS de Candelaria, Tenerife, Spain. 7Research Unit, Hospital Universitario NS de Candelaria, Tenerife, Spain. 8Institute of Medical Science, University of Toronto, Toronto, ON, Canada. 9Respiratory and Critical Care Research Group, Toronto General Research Institute, University Health Network, Toronto, ON, Canada. 10Keenan Research Center for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada. 11Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
authors: Nuria E
authors: NE
authors: Cabrera-Benítez
authors: Francisco
authors: F
authors: Valladares
authors: Sonia
authors: S
authors: García-Hernández
authors: Ángela
authors: Á
authors: Ramos-Nuez
authors: José L
authors: JL
authors: Martín-Barrasa
authors: María-Teresa
authors: MT
authors: Martínez-Saavedra
authors: Carlos
authors: C
authors: Rodríguez-Gallego
authors: Mercedes
authors: M
authors: Muros
authors: Carlos
authors: C
authors: Flores
authors: Mingyao
authors: M
authors: Liu
authors: Arthur S
authors: AS
authors: Slutsky
authors: Jesús
authors: J
authors: Villar
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology; D008297:Male; D011446:Prospective Studies; D011659:Pulmonary Gas Exchange; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013990:Tidal Volume; D055397:Ventilator-Induced Lung Injury / Q000503:physiopathology*
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; C568779:ESAM protein, human