{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["8(8)"],"submitter":["Bruells CS"],"pubmed_abstract":["<h4>Objective</h4>Mechanical ventilation (MV) is a life saving intervention for patients with respiratory failure. Even after 6 hours of MV, diaphragm atrophy and dysfunction (collectively referred to as ventilator-induced diaphragmatic dysfunction, VIDD) occurs in concert with a blunted blood flow and oxygen delivery. The regulation of hypoxia sensitive factors (i.e. hypoxia inducible factor 1α, 2α (HIF-1α,-2α), vascular endothelial growth factor (VEGF)) and angio-neogenetic factors (angiopoietin 1-3, Ang) might contribute to reactive and compensatory alterations in diaphragm muscle.<h4>Methods</h4>Male Wistar rats (n = 8) were ventilated for 24 hours or directly sacrificed (n = 8), diaphragm and mixed gastrocnemius muscle tissue was removed. Quantitative real time PCR and western blot analyses were performed to detect changes in angio-neogenetic factors and inflammatory markers. Tissues were stained using Isolectin (IB 4) to determine capillarity and calculate the capillary/fiber ratio.<h4>Results</h4>MV resulted in up-regulation of Ang 2 and HIF-1α mRNA in both diaphragm and gastrocnemius, while VEGF mRNA was down-regulated in both tissues. HIF-2α mRNA was reduced in both tissues, while GLUT 4 mRNA was increased in gastrocnemius and reduced in diaphragm samples. Protein levels of VEGF, HIF-1α, -2α and 4 did not change significantly. Additionally, inflammatory cytokine mRNA (Interleukin (IL)-6, IL-1β and TNF α) were elevated in diaphragm tissue.<h4>Conclusion</h4>The results demonstrate that 24 hrs of MV and the associated limb disuse induce an up-regulation of angio-neogenetic factors that are connected to HIF-1α. Changes in HIF-1α expression may be due to several interactions occurring during MV."],"journal":["PloS one"],"pagination":["e70524"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3738548"],"repository":["biostudies-literature"],"pubmed_title":["Prolonged mechanical ventilation alters the expression pattern of angio-neogenetic factors in a pre-clinical rat model."],"pmcid":["PMC3738548"],"pubmed_authors":["Loetscher U","Cielen N","Bruells CS","Weis J","Gayan-Ramirez G","Maes K","Dreier A","Bleilevens C","Rossaint R","Thomas D","Bergs I","Behnke BJ"],"additional_accession":[]},"is_claimable":false,"name":"Prolonged mechanical ventilation alters the expression pattern of angio-neogenetic factors in a pre-clinical rat model.","description":"<h4>Objective</h4>Mechanical ventilation (MV) is a life saving intervention for patients with respiratory failure. Even after 6 hours of MV, diaphragm atrophy and dysfunction (collectively referred to as ventilator-induced diaphragmatic dysfunction, VIDD) occurs in concert with a blunted blood flow and oxygen delivery. The regulation of hypoxia sensitive factors (i.e. hypoxia inducible factor 1α, 2α (HIF-1α,-2α), vascular endothelial growth factor (VEGF)) and angio-neogenetic factors (angiopoietin 1-3, Ang) might contribute to reactive and compensatory alterations in diaphragm muscle.<h4>Methods</h4>Male Wistar rats (n = 8) were ventilated for 24 hours or directly sacrificed (n = 8), diaphragm and mixed gastrocnemius muscle tissue was removed. Quantitative real time PCR and western blot analyses were performed to detect changes in angio-neogenetic factors and inflammatory markers. Tissues were stained using Isolectin (IB 4) to determine capillarity and calculate the capillary/fiber ratio.<h4>Results</h4>MV resulted in up-regulation of Ang 2 and HIF-1α mRNA in both diaphragm and gastrocnemius, while VEGF mRNA was down-regulated in both tissues. HIF-2α mRNA was reduced in both tissues, while GLUT 4 mRNA was increased in gastrocnemius and reduced in diaphragm samples. Protein levels of VEGF, HIF-1α, -2α and 4 did not change significantly. Additionally, inflammatory cytokine mRNA (Interleukin (IL)-6, IL-1β and TNF α) were elevated in diaphragm tissue.<h4>Conclusion</h4>The results demonstrate that 24 hrs of MV and the associated limb disuse induce an up-regulation of angio-neogenetic factors that are connected to HIF-1α. Changes in HIF-1α expression may be due to several interactions occurring during MV.","dates":{"release":"2013-01-01T00:00:00Z","publication":"2013","modification":"2025-04-18T18:27:00.72Z","creation":"2019-03-26T23:15:14Z"},"accession":"S-EPMC3738548","cross_references":{"pubmed":["23950950"],"doi":["10.1371/journal.pone.0070524"]}}