Conditional Plasminogen Activator Inhibitor Type 1 Deletion in the Endothelial Compartment Has No Beneficial Effect on Radiation-Induced Whole-Lung Damage in Mice

Publication date: 15 November 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 99, Issue 4
Author(s): Jérémy Lavigne, Frédéric Soysouvanh, Valérie Buard, Georges Tarlet, Olivier Guipaud, Vincent Paget, Fabien Milliat, Agnès François
PurposeTo investigate whether the endothelial pool of plasminogen activator inhibitor type 1 (PAI-1) plays a role in the development of radiation-induced lung damage, as previously demonstrated in the intestine.Methods and MaterialsHuman lung microvascular endothelial cells were exposed to 10 Gy irradiation so as to study their ability to acquire an "activated" phenotype. Mice in which the Cre-Lox strategy was used to produce PAI-1 deletion specifically in the endothelial compartment were exposed to 17 Gy whole-thorax irradiation and followed up for 2, 13, and 23 weeks after irradiation.ResultsHuman lung microvascular endothelial cells had an activated phenotype after radiation exposure, overexpressed PAI-1, and underwent endothelial-to-mesenchymal transition. In mice, knockout of PAI-1 in the endothelium had no beneficial effect on radiation-induced lung damage and showed a tendency to worsen acute lesions.ConclusionsAs opposed to the intestine, the endothelial pool of PAI-1 does not play a determinant role in the development of radiation-induced lung damage. The therapeutic value of PAI-1 inhibition in lung radiation injury may be associated with other types of cells.



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