Elevated Plasma Angiopoietin-2 Levels and Primary Graft Dysfunction after Lung Transplantation

Joshua M. Diamond, Mary K. Porteous, Edward Cantu, Nuala J. Meyer, Rupal J. Shah, David J. Lederer, Steven M. Kawut, James Lee, Scarlett L. Bellamy, Scott M. Palmer, Vibha N. Lama, Sangeeta M. Bhorade, Maria Crespo, Ejigayehu Demissie, Keith Wille, Jonathan Orens, Pali D. Shah, Ann Weinacker, David Weill, Selim ArcasoyDavid S. Wilkes, Lorraine B. Ware, Jason D. Christie

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Article numbere51932
JournalPloS one
Volume7
Issue number12
DOIs
StatePublished - Dec 19 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Diamond, J. M., Porteous, M. K., Cantu, E., Meyer, N. J., Shah, R. J., Lederer, D. J., Kawut, S. M., Lee, J., Bellamy, S. L., Palmer, S. M., Lama, V. N., Bhorade, S. M., Crespo, M., Demissie, E., Wille, K., Orens, J., Shah, P. D., Weinacker, A., Weill, D., ... Christie, J. D. (2012). Elevated Plasma Angiopoietin-2 Levels and Primary Graft Dysfunction after Lung Transplantation. PloS one, 7(12), [e51932]. https://doi.org/10.1371/journal.pone.0051932