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

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 Ti...

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Autores principales: Diamond, Joshua M., Porteous, Mary K., Cantu, Edward, Meyer, Nuala J., Shah, Rupal J., Lederer, David J., Kawut, Steven M., Lee, James, Bellamy, Scarlett L., Palmer, Scott M., Lama, Vibha N., Bhorade, Sangeeta M., Crespo, Maria, Demissie, Ejigayehu, Wille, Keith, Orens, Jonathan, Shah, Pali D., Weinacker, Ann, Weill, David, Arcasoy, Selim, Wilkes, David S., Ware, Lorraine B., Christie, Jason D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526525/
https://www.ncbi.nlm.nih.gov/pubmed/23284823
http://dx.doi.org/10.1371/journal.pone.0051932
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author Diamond, Joshua M.
Porteous, Mary K.
Cantu, Edward
Meyer, Nuala J.
Shah, Rupal J.
Lederer, David J.
Kawut, Steven M.
Lee, James
Bellamy, Scarlett L.
Palmer, Scott M.
Lama, Vibha N.
Bhorade, Sangeeta M.
Crespo, Maria
Demissie, Ejigayehu
Wille, Keith
Orens, Jonathan
Shah, Pali D.
Weinacker, Ann
Weill, David
Arcasoy, Selim
Wilkes, David S.
Ware, Lorraine B.
Christie, Jason D.
author_facet Diamond, Joshua M.
Porteous, Mary K.
Cantu, Edward
Meyer, Nuala J.
Shah, Rupal J.
Lederer, David J.
Kawut, Steven M.
Lee, James
Bellamy, Scarlett L.
Palmer, Scott M.
Lama, Vibha N.
Bhorade, Sangeeta M.
Crespo, Maria
Demissie, Ejigayehu
Wille, Keith
Orens, Jonathan
Shah, Pali D.
Weinacker, Ann
Weill, David
Arcasoy, Selim
Wilkes, David S.
Ware, Lorraine B.
Christie, Jason D.
author_sort Diamond, Joshua M.
collection PubMed
description 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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spelling pubmed-35265252013-01-02 Elevated Plasma Angiopoietin-2 Levels and Primary Graft Dysfunction after Lung Transplantation Diamond, Joshua M. Porteous, Mary K. Cantu, Edward Meyer, Nuala J. Shah, Rupal J. Lederer, David J. Kawut, Steven M. Lee, James Bellamy, Scarlett L. Palmer, Scott M. Lama, Vibha N. Bhorade, Sangeeta M. Crespo, Maria Demissie, Ejigayehu Wille, Keith Orens, Jonathan Shah, Pali D. Weinacker, Ann Weill, David Arcasoy, Selim Wilkes, David S. Ware, Lorraine B. Christie, Jason D. PLoS One Research Article 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. Public Library of Science 2012-12-19 /pmc/articles/PMC3526525/ /pubmed/23284823 http://dx.doi.org/10.1371/journal.pone.0051932 Text en © 2012 Diamond et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Diamond, Joshua M.
Porteous, Mary K.
Cantu, Edward
Meyer, Nuala J.
Shah, Rupal J.
Lederer, David J.
Kawut, Steven M.
Lee, James
Bellamy, Scarlett L.
Palmer, Scott M.
Lama, Vibha N.
Bhorade, Sangeeta M.
Crespo, Maria
Demissie, Ejigayehu
Wille, Keith
Orens, Jonathan
Shah, Pali D.
Weinacker, Ann
Weill, David
Arcasoy, Selim
Wilkes, David S.
Ware, Lorraine B.
Christie, Jason D.
Elevated Plasma Angiopoietin-2 Levels and Primary Graft Dysfunction after Lung Transplantation
title Elevated Plasma Angiopoietin-2 Levels and Primary Graft Dysfunction after Lung Transplantation
title_full Elevated Plasma Angiopoietin-2 Levels and Primary Graft Dysfunction after Lung Transplantation
title_fullStr Elevated Plasma Angiopoietin-2 Levels and Primary Graft Dysfunction after Lung Transplantation
title_full_unstemmed Elevated Plasma Angiopoietin-2 Levels and Primary Graft Dysfunction after Lung Transplantation
title_short Elevated Plasma Angiopoietin-2 Levels and Primary Graft Dysfunction after Lung Transplantation
title_sort elevated plasma angiopoietin-2 levels and primary graft dysfunction after lung transplantation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526525/
https://www.ncbi.nlm.nih.gov/pubmed/23284823
http://dx.doi.org/10.1371/journal.pone.0051932
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