Assessment of Predictive Biomarkers Associated with Ischemia/Reperfusion Injury and Primary Graft Dysfunction in Lung Transplants
| Autor: | A. Dagenais, Emmanuelle Brochiero, C. Landry, A. Privé, Yves Berthiaume, Claude Poirier, Damien Adam, Jean-François Cailhier, Jean-Francois Germain, Ahmed Menaouar, M. Merjaneh, Nicolas Noiseux, Pasquale Ferraro |
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| Rok vydání: | 2019 |
| Předmět: |
Pulmonary and Respiratory Medicine
Epithelial sodium channel Transplantation Pathology medicine.medical_specialty Lung business.industry medicine.medical_treatment Ischemia Primary Graft Dysfunction Inflammation respiratory system medicine.disease Epithelial Damage medicine.anatomical_structure medicine Lung transplantation Surgery medicine.symptom Cardiology and Cardiovascular Medicine business Reperfusion injury |
| Zdroj: | The Journal of Heart and Lung Transplantation. 38:S239-S240 |
| ISSN: | 1053-2498 |
| DOI: | 10.1016/j.healun.2019.01.590 |
| Popis: | Purpose Ischemia reperfusion (I/R) is a major cause of primary graft dysfunction (PGD) after lung transplantation. I/R and PGD feature endothelial/alveolar epithelial damage, lung edema and inflammation. Edema resorption depends on the restoration of alveolar integrity and its ability to reabsorb Na+ (ENaC) and fluid. We hypothesized that alveolar epithelial damage and repair are critical in PGD pathophysiology and resolution. Our aim is to identify novel markers and therapeutic targets associated with I/R using cellular and animal models as well as human samples from lung transplants. Methods Mimicking I/R protocol was used to evaluate alveolar epithelial barrier integrity and capacity of wound healing in primary cultures of rat's alveolar epithelial cells. These cell cultures were then treated with an activator of K+ channel (KvLQT1). In a porcine model of ischemia/ex-vivo reperfusion, an inflammatory stress was induced by i.v. infusion with LPS. Finally, samples were collected from 38 lung transplant patients. Results In primary cell cultures, we showed altered ENaC and tight junction protein (ZO-1) expression after injury. A decline in transepithelial resistance (TER) and altered alveolar wound repair rates were also observed following the mimicking I/R protocol. Treatment with K+ channel activator (R-L3) showed enhanced repair rates, barrier integrity (higher TER, ZO-1 staining) and ENaC expression. In our porcine model, lung damage and edema was observed as well as exacerbated inflammatory response and decreased ENaC expression. Preliminary data from lung transplant samples indicated an inflammatory response and decreased ENaC and ZO-1 expression in patients with PGD. Conclusion Our data support the hypothesis of alveolar epithelial dysfunction after I/R injury. We will now investigate a potential correlation between levels of inflammatory molecules and epithelial damage markers in bronchoalveolar lavages and blood samples (at different time-points) from lung transplants with various PGD scores. |
| Databáze: | OpenAIRE |
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