title: Soluble platelet-endothelial cell adhesion molecule-1, a biomarker of ventilator-induced lung injury.
abstract: BACKGROUND
  Endothelial cell injury is an important component of acute lung injury. Platelet-endothelial cell adhesion molecule-1 (PECAM1) is a transmembrane protein that connects endothelial cells to one another and can be detected as a soluble, truncated protein (sPECAM1) in serum. We hypothesized that injurious mechanical ventilation (MV) leads to shedding of PECAM1 from lung endothelial cells resulting in increasing sPECAM1 levels in the systemic circulation.
  
  
  METHODS
  We studied 36 Sprague-Dawley rats in two prospective, randomized, controlled studies (healthy and septic) using established animal models of ventilator-induced lung injury. Animals (n = 6 in each group) were randomized to spontaneous breathing or two MV strategies: low tidal volume (VT) (6 ml/kg) and high-VT (20 ml/kg) on 2 cmH2O of positive end-expiratory pressure (PEEP). In low-VT septic animals, 10 cmH2O of PEEP was applied. We performed pulmonary histological and physiological evaluation and measured lung PECAM1 protein content and serum sPECAM1 levels after four hours ventilation period.
  
  
  RESULTS
  High-VT MV caused severe lung injury in healthy and septic animals, and decreased lung PECAM1 protein content (P < 0.001). Animals on high-VT had a four- to six-fold increase of mean sPECAM1 serum levels than the unventilated counterpart (35.4 ± 10.4 versus 5.6 ± 1.7 ng/ml in healthy rats; 156.8 ± 47.6 versus 35.6 ± 12.6 ng/ml in septic rats) (P < 0.0001). Low-VT MV prevented these changes. Levels of sPECAM1 in healthy animals on high-VT MV paralleled the sPECAM1 levels of non-ventilated septic animals.
  
  
  CONCLUSIONS
  Our findings suggest that circulating sPECAM1 may represent a promising biomarker for the detection and monitoring of ventilator-induced lung injury.
authors.forename: Jesús
authors.initials: J
authors.lastname: Villar
authors.forename: Mercedes
authors.initials: M
authors.lastname: Muros
authors.forename: Nuria E
authors.initials: NE
authors.lastname: Cabrera-Benítez
authors.forename: Francisco
authors.initials: F
authors.lastname: Valladares
authors.forename: Milagros
authors.initials: M
authors.lastname: López-Hernández
authors.forename: Carlos
authors.initials: C
authors.lastname: Flores
authors.forename: José L
authors.initials: JL
authors.lastname: Martín-Barrasa
authors.forename: Jesús
authors.initials: J
authors.lastname: Blanco
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.forename: Robert M
authors.initials: RM
authors.lastname: Kacmarek
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood*; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D055397:Ventilator-Induced Lung Injury / Q000097:blood* / Q000473:pathology*
chemical_list: D015415:Biomarkers; D019408:Platelet Endothelial Cell Adhesion Molecule-1