TY - JOUR
T1 - Late proliferating and inflammatory effects on murine microvascular heart and lung endothelial cells after irradiation
AU - Sievert, Wolfgang
AU - Trott, Klaus Rüdiger
AU - Azimzadeh, Omid
AU - Tapio, Soile
AU - Zitzelsberger, Horst
AU - Multhoff, Gabriele
N1 - Publisher Copyright:
© 2015 Elsevier Ireland Ltd.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - Endothelial cells
KW - Endothelial progenitor cells
KW - Inflammation
KW - Irradiation
KW - Proliferation
UR - http://www.scopus.com/inward/record.url?scp=84952637542&partnerID=8YFLogxK
U2 - 10.1016/j.radonc.2015.07.029
DO - 10.1016/j.radonc.2015.07.029
M3 - Article
C2 - 26233589
AN - SCOPUS:84952637542
SN - 0167-8140
VL - 117
SP - 376
EP - 381
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
IS - 2
ER -