Transient heat stress protects from severe endothelial damage and dysfunction during prolonged experimental ex-vivo lung perfusion
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| Názov: | Transient heat stress protects from severe endothelial damage and dysfunction during prolonged experimental ex-vivo lung perfusion |
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| Autori: | Roumen Parapanov, Anne Debonneville, Manon Allouche, Jérôme Lugrin, Helena Rodriguez-Caro, Lucas Liaudet, Thorsten Krueger |
| Zdroj: | Front Immunol Frontiers in Immunology, Vol 15 (2024) Frontiers in immunology, vol. 15, pp. 1390026 |
| Informácie o vydavateľovi: | Frontiers Media SA, 2024. |
| Rok vydania: | 2024 |
| Predmety: | Male, 0301 basic medicine, 0303 health sciences, animal model, Immunology, RC581-607, Rats, 3. Good health, Perfusion, Platelet Endothelial Cell Adhesion Molecule-1, 03 medical and health sciences, heat shock response, ex-vivo lung perfusion, pulmonary endothelium, lung ischemia-reperfusion, Reperfusion Injury, lung transplantation, Animals, Lung/pathology, Lung/metabolism, Heat-Shock Response, Perfusion/methods, Reperfusion Injury/metabolism, Reperfusion Injury/prevention & control, Lung Transplantation/adverse effects, Endothelium, Vascular/metabolism, Endothelium, Vascular/pathology, Platelet Endothelial Cell Adhesion Molecule-1/metabolism, heat therapy, Endothelium, Vascular, Immunologic diseases. Allergy, Lung, Lung Transplantation |
| Popis: | IntroductionThe pulmonary endothelium is the primary target of lung ischemia-reperfusion injury leading to primary graft dysfunction after lung transplantation. We hypothesized that treating damaged rat lungs by a transient heat stress during ex-vivo lung perfusion (EVLP) to elicit a pulmonary heat shock response could protect the endothelium from severe reperfusion injury.MethodsRat lungs damaged by 1h warm ischemia were reperfused on an EVLP platform for up to 6h at a constant temperature (T°) of 37°C (EVLP37°C group), or following a transient heat stress (HS) at 41.5°C from 1 to 1.5h of EVLP (EVLPHS group). A group of lungs exposed to 1h EVLP only (pre-heating conditions) was added as control (Baseline group). In a first protocol, we measured lung heat sock protein expression (HSP70, HSP27 and Hsc70) at selected time-points (n=5/group at each time). In a second protocol, we determined (n=5/group) lung weight gain (edema), pulmonary compliance, oxygenation capacity, pulmonary artery pressure (PAP) and vascular resistance (PVR), the expression of PECAM-1 (CD31) and phosphorylation status of Src-kinase and VE-cadherin in lung tissue, as well as the release in perfusate of cytokines (TNFα, IL-1β) and endothelial biomarkers (sPECAM, von Willebrand Factor -vWF-, sE-selectin and sICAM-1). Histological and immunofluorescent studies assessed perivascular edema and formation of 3-nitrotyrosine (a marker of peroxinitrite) in CD31 lung endothelium.ResultsHS induced an early (3h) and persisting expression of HSP70 and HSP27, without influencing Hsc70. Lungs from the EVLP37°C group developed massive edema, low compliance and oxygenation, elevated PAP and PVR, substantial release of TNFα, IL-1β, s-PECAM, vWF, E-selectin and s-ICAM, as well as significant Src-kinase activation, VE-cadherin phosphorylation, endothelial 3-NT formation and reduced CD31 expression. In marked contrast, all these alterations were either abrogated or significantly attenuated by HS treatment.ConclusionThe therapeutic application of a transient heat stress during EVLP of damaged rat lungs reduces endothelial permeability, attenuates pulmonary vasoconstriction, prevents src-kinase activation and VE-cadherin phosphorylation, while reducing endothelial peroxinitrite generation and the release of cytokines and endothelial biomarkers. Collectively, these data demonstrate that therapeutic heat stress may represent a promising strategy to protect the lung endothelium from severe reperfusion injury. |
| Druh dokumentu: | Article Other literature type |
| Popis súboru: | application/pdf |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2024.1390026 |
| Prístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/38807604 https://doaj.org/article/cf331092e980411e8e7d540934261cfb https://serval.unil.ch/notice/serval:BIB_3B26095DE465 http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_3B26095DE4650 https://serval.unil.ch/resource/serval:BIB_3B26095DE465.P001/REF.pdf |
| Rights: | CC BY |
| Prístupové číslo: | edsair.doi.dedup.....303c169034924bf2d9c81e87c764af35 |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | IntroductionThe pulmonary endothelium is the primary target of lung ischemia-reperfusion injury leading to primary graft dysfunction after lung transplantation. We hypothesized that treating damaged rat lungs by a transient heat stress during ex-vivo lung perfusion (EVLP) to elicit a pulmonary heat shock response could protect the endothelium from severe reperfusion injury.MethodsRat lungs damaged by 1h warm ischemia were reperfused on an EVLP platform for up to 6h at a constant temperature (T°) of 37°C (EVLP37°C group), or following a transient heat stress (HS) at 41.5°C from 1 to 1.5h of EVLP (EVLPHS group). A group of lungs exposed to 1h EVLP only (pre-heating conditions) was added as control (Baseline group). In a first protocol, we measured lung heat sock protein expression (HSP70, HSP27 and Hsc70) at selected time-points (n=5/group at each time). In a second protocol, we determined (n=5/group) lung weight gain (edema), pulmonary compliance, oxygenation capacity, pulmonary artery pressure (PAP) and vascular resistance (PVR), the expression of PECAM-1 (CD31) and phosphorylation status of Src-kinase and VE-cadherin in lung tissue, as well as the release in perfusate of cytokines (TNFα, IL-1β) and endothelial biomarkers (sPECAM, von Willebrand Factor -vWF-, sE-selectin and sICAM-1). Histological and immunofluorescent studies assessed perivascular edema and formation of 3-nitrotyrosine (a marker of peroxinitrite) in CD31 lung endothelium.ResultsHS induced an early (3h) and persisting expression of HSP70 and HSP27, without influencing Hsc70. Lungs from the EVLP37°C group developed massive edema, low compliance and oxygenation, elevated PAP and PVR, substantial release of TNFα, IL-1β, s-PECAM, vWF, E-selectin and s-ICAM, as well as significant Src-kinase activation, VE-cadherin phosphorylation, endothelial 3-NT formation and reduced CD31 expression. In marked contrast, all these alterations were either abrogated or significantly attenuated by HS treatment.ConclusionThe therapeutic application of a transient heat stress during EVLP of damaged rat lungs reduces endothelial permeability, attenuates pulmonary vasoconstriction, prevents src-kinase activation and VE-cadherin phosphorylation, while reducing endothelial peroxinitrite generation and the release of cytokines and endothelial biomarkers. Collectively, these data demonstrate that therapeutic heat stress may represent a promising strategy to protect the lung endothelium from severe reperfusion injury. |
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| ISSN: | 16643224 |
| DOI: | 10.3389/fimmu.2024.1390026 |