Angiopoietin-1 treatment reduces inflammation but does not prevent ventilator-induced lung injury.
<h4>Background</h4>Loss of integrity of the epithelial and endothelial barriers is thought to be a prominent feature of ventilator-induced lung injury (VILI). Based on its function in vascular integrity, we hypothesize that the angiopoietin (Ang)-Tie2 system plays a role in the developme...
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Public Library of Science (PLoS)
2010
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oai:doaj.org-article:7f07545ec1b245ada89475e5a61b90172021-11-18T07:01:43ZAngiopoietin-1 treatment reduces inflammation but does not prevent ventilator-induced lung injury.1932-620310.1371/journal.pone.0015653https://doaj.org/article/7f07545ec1b245ada89475e5a61b90172010-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21179479/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Loss of integrity of the epithelial and endothelial barriers is thought to be a prominent feature of ventilator-induced lung injury (VILI). Based on its function in vascular integrity, we hypothesize that the angiopoietin (Ang)-Tie2 system plays a role in the development of VILI. The present study was designed to examine the effects of mechanical ventilation on the Ang-Tie2 system in lung tissue. Moreover, we evaluated whether treatment with Ang-1, a Tie2 receptor agonist, protects against inflammation, vascular leakage and impaired gas exchange induced by mechanical ventilation.<h4>Methods</h4>Mice were anesthetized, tracheotomized and mechanically ventilated for 5 hours with either an inspiratory pressure of 10 cmH2O ('low' tidal volume ∼7.5 ml/kg; LVT) or 18 cmH2O ('high' tidal volume ∼15 ml/kg; HVT). At initiation of HVT-ventilation, recombinant human Ang-1 was intravenously administered (1 or 4 µg per animal). Non-ventilated mice served as controls.<h4>Results</h4>HVT-ventilation influenced the Ang-Tie2 system in lungs of healthy mice since Ang-1, Ang-2 and Tie2 mRNA were decreased. Treatment with Ang-1 increased Akt-phosphorylation indicating Tie2 signaling. Ang-1 treatment reduced infiltration of granulocytes and expression of keratinocyte-derived chemokine (KC), macrophage inflammatory protein (MIP)-2, monocyte chemotactic protein (MCP)-1 and interleukin (IL)-1β caused by HVT-ventilation. Importantly, Ang-1 treatment did not prevent vascular leakage and impaired gas exchange in HVT-ventilated mice despite inhibition of inflammation, vascular endothelial growth factor (VEGF) and Ang-2 expression.<h4>Conclusions</h4>Ang-1 treatment downregulates pulmonary inflammation, VEGF and Ang-2 expression but does not protect against vascular leakage and impaired gas exchange induced by HVT-ventilation.Maria A HegemanMarije P HennusMatijs van MeursPieter M CobelensAnnemieke KavelaarsNicolaas J JansenMarcus J SchultzAdrianus J van VughtGrietje MolemaCobi J HeijnenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 12, p e15653 (2010) |
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| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Maria A Hegeman Marije P Hennus Matijs van Meurs Pieter M Cobelens Annemieke Kavelaars Nicolaas J Jansen Marcus J Schultz Adrianus J van Vught Grietje Molema Cobi J Heijnen Angiopoietin-1 treatment reduces inflammation but does not prevent ventilator-induced lung injury. |
| description |
<h4>Background</h4>Loss of integrity of the epithelial and endothelial barriers is thought to be a prominent feature of ventilator-induced lung injury (VILI). Based on its function in vascular integrity, we hypothesize that the angiopoietin (Ang)-Tie2 system plays a role in the development of VILI. The present study was designed to examine the effects of mechanical ventilation on the Ang-Tie2 system in lung tissue. Moreover, we evaluated whether treatment with Ang-1, a Tie2 receptor agonist, protects against inflammation, vascular leakage and impaired gas exchange induced by mechanical ventilation.<h4>Methods</h4>Mice were anesthetized, tracheotomized and mechanically ventilated for 5 hours with either an inspiratory pressure of 10 cmH2O ('low' tidal volume ∼7.5 ml/kg; LVT) or 18 cmH2O ('high' tidal volume ∼15 ml/kg; HVT). At initiation of HVT-ventilation, recombinant human Ang-1 was intravenously administered (1 or 4 µg per animal). Non-ventilated mice served as controls.<h4>Results</h4>HVT-ventilation influenced the Ang-Tie2 system in lungs of healthy mice since Ang-1, Ang-2 and Tie2 mRNA were decreased. Treatment with Ang-1 increased Akt-phosphorylation indicating Tie2 signaling. Ang-1 treatment reduced infiltration of granulocytes and expression of keratinocyte-derived chemokine (KC), macrophage inflammatory protein (MIP)-2, monocyte chemotactic protein (MCP)-1 and interleukin (IL)-1β caused by HVT-ventilation. Importantly, Ang-1 treatment did not prevent vascular leakage and impaired gas exchange in HVT-ventilated mice despite inhibition of inflammation, vascular endothelial growth factor (VEGF) and Ang-2 expression.<h4>Conclusions</h4>Ang-1 treatment downregulates pulmonary inflammation, VEGF and Ang-2 expression but does not protect against vascular leakage and impaired gas exchange induced by HVT-ventilation. |
| format |
article |
| author |
Maria A Hegeman Marije P Hennus Matijs van Meurs Pieter M Cobelens Annemieke Kavelaars Nicolaas J Jansen Marcus J Schultz Adrianus J van Vught Grietje Molema Cobi J Heijnen |
| author_facet |
Maria A Hegeman Marije P Hennus Matijs van Meurs Pieter M Cobelens Annemieke Kavelaars Nicolaas J Jansen Marcus J Schultz Adrianus J van Vught Grietje Molema Cobi J Heijnen |
| author_sort |
Maria A Hegeman |
| title |
Angiopoietin-1 treatment reduces inflammation but does not prevent ventilator-induced lung injury. |
| title_short |
Angiopoietin-1 treatment reduces inflammation but does not prevent ventilator-induced lung injury. |
| title_full |
Angiopoietin-1 treatment reduces inflammation but does not prevent ventilator-induced lung injury. |
| title_fullStr |
Angiopoietin-1 treatment reduces inflammation but does not prevent ventilator-induced lung injury. |
| title_full_unstemmed |
Angiopoietin-1 treatment reduces inflammation but does not prevent ventilator-induced lung injury. |
| title_sort |
angiopoietin-1 treatment reduces inflammation but does not prevent ventilator-induced lung injury. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/7f07545ec1b245ada89475e5a61b9017 |
| work_keys_str_mv |
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