Late proliferating and inflammatory effects on murine microvascular heart and lung endothelial cells after irradiation

Radiother Oncol. 2015 Nov;117(2):376-81. doi: 10.1016/j.radonc.2015.07.029. Epub 2015 Jul 29.

Abstract

Background and purpose: 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).

Material and 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.

Keywords: Atherosclerosis; Endothelial cells; Endothelial progenitor cells; Inflammation; Irradiation; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / radiation effects*
  • Cells, Cultured
  • Endothelial Cells / radiation effects*
  • Female
  • Flow Cytometry
  • Heart / radiation effects*
  • Inflammation / physiopathology*
  • Lung / radiation effects*
  • Mice
  • Mice, Inbred C57BL
  • Microvessels / physiopathology*
  • Radiotherapy Dosage
  • Thorax / radiation effects
  • Up-Regulation / radiation effects