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

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• 作者：Wolfgang Sievert^a ; Klaus-Rü ; diger Trott^b ; Omid Azimzadeh^c ; Soile Tapio^c ; Horst Zitzelsberger^d ; Gabriele Multhoff^a ; ^{gabriele.multhoff@lrz.tu-muenchen.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Irradiation ; Endothelial cells ; Proliferation ; Endothelial progenitor cells ; Inflammation ; Atherosclerosis
• 刊名：Radiotherapy and Oncology
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：117
• 期：2
• 页码：376-381
• 全文大小：969 K

文摘

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.