title: Late proliferating and inflammatory effects on murine microvascular heart and lung endothelial cells after irradiation.
abstract: OBJECTIVE
  Radiotherapy of thoracic tumors increases the risk to develop cardiac diseases at later time-points. We compared time kinetics of radiation-induced changes of surface markers related to proliferation, progenitor cell development and inflammation in lung and heart microvascular endothelial cells (ECs).
  
  
  METHODS
  Mice received local thorax irradiation with a single dose of 0, 2 or 8 Gy. Following magnetic bead separation and biotin-streptavidin competition, cell surface markers of isolated ECs from the lung and heart were analyzed 5, 10, 15 and 20 weeks after irradiation by flow cytometry.
  
  
  RESULTS
  Irradiation with 8 Gy resulted in a temporary and differential up-regulation of proliferation markers (HCAM, Integrin β-3, Endoglin, VE-cadherin, VEGFR-2) on ECs. Mucosialin a progenitor marker increased in lung ECs 15-20 weeks and inflammatory markers (PECAM-1, ICAM-1, ICAM-2, VCAM-1) started to increase 10 weeks after thorax irradiation with 8 Gy. Interestingly, ICAM-1 and VCAM-1 remained up-regulated 20 weeks after irradiation in heart and lung ECs.
  
  
  CONCLUSIONS
  The persistently elevated expression density of ICAM-1 and VCAM-1 on ECs may suggest that an irradiation at 8 Gy induces late inflammatory responses in heart and lung ECs.
authors.affiliation: Department of Radiation Oncology, Technische Universität München, Helmholtz Zentrum München (HMGU), German Research Center for Environmental Health Munich, Neuherberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sievert
authors.affiliation: Department of Oncology, Imperial University College London, UK.
authors.forename: Klaus-Rüdiger
authors.initials: KR
authors.lastname: Trott
authors.affiliation: Institute of Radiation Biology, Helmholtz Zentrum München (HMGU), German Research Center for Environmental Health Munich, Neuherberg, Germany.
authors.forename: Omid
authors.initials: O
authors.lastname: Azimzadeh
authors.affiliation: Institute of Radiation Biology, Helmholtz Zentrum München (HMGU), German Research Center for Environmental Health Munich, Neuherberg, Germany.
authors.forename: Soile
authors.initials: S
authors.lastname: Tapio
authors.affiliation: Research Unit Radiation Cytogenetics, Helmholtz Zentrum München (HMGU), German Research Center for Environmental Health Munich, Neuherberg, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Zitzelsberger
authors.affiliation: Department of Radiation Oncology, Technische Universität München, Helmholtz Zentrum München (HMGU), German Research Center for Environmental Health Munich, Neuherberg, Germany. Electronic address: gabriele.multhoff@lrz.tu-muenchen.de.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Multhoff
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000528:radiation effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000528:radiation effects*; D005260:Female; D005434:Flow Cytometry; D006321:Heart / Q000528:radiation effects*; D007249:Inflammation / Q000503:physiopathology*; D008168:Lung / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000503:physiopathology*; D011879:Radiotherapy Dosage; D013909:Thorax / Q000528:radiation effects; D015854:Up-Regulation / Q000528:radiation effects
keywords: Atherosclerosis; Endothelial cells; Endothelial progenitor cells; Inflammation; Irradiation; Proliferation