title: Elevated plasma angiopoietin-2 levels and primary graft dysfunction after lung transplantation.
abstract: BACKGROUND
  Primary graft dysfunction (PGD) is a significant contributor to early morbidity and mortality after lung transplantation. Increased vascular permeability in the allograft has been identified as a possible mechanism leading to PGD. Angiopoietin-2 serves as a partial antagonist to the Tie-2 receptor and induces increased endothelial permeability. We hypothesized that elevated Ang2 levels would be associated with development of PGD.
  
  
  METHODS
  We performed a case-control study, nested within the multi-center Lung Transplant Outcomes Group cohort. Plasma angiopoietin-2 levels were measured pre-transplant and 6 and 24 hours post-reperfusion. The primary outcome was development of grade 3 PGD in the first 72 hours. The association of angiopoietin-2 plasma levels and PGD was evaluated using generalized estimating equations (GEE).
  
  
  RESULTS
  There were 40 PGD subjects and 79 non-PGD subjects included for analysis. Twenty-four PGD subjects (40%) and 47 non-PGD subjects (59%) received a transplant for the diagnosis of idiopathic pulmonary fibrosis (IPF). Among all subjects, GEE modeling identified a significant change in angiopoietin-2 level over time in cases compared to controls (p = 0.03). The association between change in angiopoietin-2 level over the perioperative time period was most significant in patients with a pre-operative diagnosis of IPF (p = 0.02); there was no statistically significant correlation between angiopoietin-2 plasma levels and the development of PGD in the subset of patients transplanted for chronic obstructive pulmonary disease (COPD) (p = 0.9).
  
  
  CONCLUSIONS
  Angiopoietin-2 levels were significantly associated with the development of PGD after lung transplantation. Further studies examining the regulation of endothelial cell permeability in the pathogenesis of PGD are indicated.
authors.affiliation: Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. joshua.diamond@uphs.upenn.edu
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Diamond
authors.forename: Mary K
authors.initials: MK
authors.lastname: Porteous
authors.forename: Edward
authors.initials: E
authors.lastname: Cantu
authors.forename: Nuala J
authors.initials: NJ
authors.lastname: Meyer
authors.forename: Rupal J
authors.initials: RJ
authors.lastname: Shah
authors.forename: David J
authors.initials: DJ
authors.lastname: Lederer
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kawut
authors.forename: James
authors.initials: J
authors.lastname: Lee
authors.forename: Scarlett L
authors.initials: SL
authors.lastname: Bellamy
authors.forename: Scott M
authors.initials: SM
authors.lastname: Palmer
authors.forename: Vibha N
authors.initials: VN
authors.lastname: Lama
authors.forename: Sangeeta M
authors.initials: SM
authors.lastname: Bhorade
authors.forename: Maria
authors.initials: M
authors.lastname: Crespo
authors.forename: Ejigayehu
authors.initials: E
authors.lastname: Demissie
authors.forename: Keith
authors.initials: K
authors.lastname: Wille
authors.forename: Jonathan
authors.initials: J
authors.lastname: Orens
authors.forename: Pali D
authors.initials: PD
authors.lastname: Shah
authors.forename: Ann
authors.initials: A
authors.lastname: Weinacker
authors.forename: David
authors.initials: D
authors.lastname: Weill
authors.forename: Selim
authors.initials: S
authors.lastname: Arcasoy
authors.forename: David S
authors.initials: DS
authors.lastname: Wilkes
authors.forename: Lorraine B
authors.initials: LB
authors.lastname: Ware
authors.forename: Jason D
authors.initials: JD
authors.lastname: Christie
mesh_terms: D042702:Angiopoietin-2 / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D055031:Primary Graft Dysfunction / Q000097:blood* / Q000209:etiology*; D013997:Time Factors
chemical_list: D042702:Angiopoietin-2