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Multicenter Study
. 2012;7(12):e51932.
doi: 10.1371/journal.pone.0051932. Epub 2012 Dec 19.

Elevated plasma angiopoietin-2 levels and primary graft dysfunction after lung transplantation

Collaborators, Affiliations
Multicenter Study

Elevated plasma angiopoietin-2 levels and primary graft dysfunction after lung transplantation

Joshua M Diamond et al. PLoS One. 2012.

Abstract

Introduction: 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Longitudinal median Angiopoietin 2 level across the pre-transplant, 6-h post-transplant, and 24-h post-transplant time points.
A) all study subjects, B) subjects with COPD, and C) subjects with IPF. Solid line represents PGD cases and dashed line represents PGD-free controls. Error bars represent the 95% CI. All p-values reported are from GEE modeling.

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