Single and fractionated ionizing radiation induce alterations in endothelial connexin expression and channel function

Research output: Contribution to journalArticle

Bibtex - Download

@article{8f2a2b6d20954cfb82769a813868577b,
title = "Single and fractionated ionizing radiation induce alterations in endothelial connexin expression and channel function",
abstract = "Radiotherapy is an effective treatment for most tumor types. However, emerging evidence indicates an increased risk for atherosclerosis after ionizing radiation exposure, initiated by endothelial cell dysfunction. Interestingly, endothelial cells express connexin (Cx) proteins that are reported to exert proatherogenic as well as atheroprotective effects. Furthermore, Cxs form channels, gap junctions and hemichannels, that are involved in bystander signaling that leads to indirect radiation effects in non-exposed cells. We here aimed to investigate the consequences of endothelial cell irradiation on Cx expression and channel function. Telomerase immortalized human Coronary Artery/Microvascular Endothelial cells were exposed to single and fractionated X-rays. Several biological endpoints were investigated at different time points after exposure: Cx gene and protein expression, gap junctional dye coupling and hemichannel function. We demonstrate that single and fractionated irradiation induce upregulation of proatherogenic Cx43 and downregulation of atheroprotective Cx40 gene and protein levels in a dose-dependent manner. Single and fractionated irradiation furthermore increased gap junctional communication and induced hemichannel opening. Our findings indicate alterations in Cx expression that are typically observed in endothelial cells covering atherosclerotic plaques. The observed radiation-induced increase in Cx channel function may promote bystander signaling thereby exacerbating endothelial cell damage and atherogenesis.",
keywords = "radiotherapy, connexin, dose fractionation, hemichannels, X-rays, endothelial cells",
author = "Raghda Ramadan and Els Vromans and Anang, {Dornatien Chuo} and Elke Decrock and Ahmed, {Mohamed Mysara} and Pieter Monsieurs and Sarah Baatout and Luc Leybaert and An Aerts",
note = "Score=10",
year = "2019",
month = "6",
day = "20",
doi = "10.1038/s41598-019-39317-9",
language = "English",
volume = "9",
pages = "1--16",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

RIS - Download

TY - JOUR

T1 - Single and fractionated ionizing radiation induce alterations in endothelial connexin expression and channel function

AU - Ramadan, Raghda

AU - Vromans, Els

AU - Anang, Dornatien Chuo

AU - Decrock, Elke

AU - Ahmed, Mohamed Mysara

AU - Monsieurs, Pieter

AU - Baatout, Sarah

AU - Leybaert, Luc

AU - Aerts, An

N1 - Score=10

PY - 2019/6/20

Y1 - 2019/6/20

N2 - Radiotherapy is an effective treatment for most tumor types. However, emerging evidence indicates an increased risk for atherosclerosis after ionizing radiation exposure, initiated by endothelial cell dysfunction. Interestingly, endothelial cells express connexin (Cx) proteins that are reported to exert proatherogenic as well as atheroprotective effects. Furthermore, Cxs form channels, gap junctions and hemichannels, that are involved in bystander signaling that leads to indirect radiation effects in non-exposed cells. We here aimed to investigate the consequences of endothelial cell irradiation on Cx expression and channel function. Telomerase immortalized human Coronary Artery/Microvascular Endothelial cells were exposed to single and fractionated X-rays. Several biological endpoints were investigated at different time points after exposure: Cx gene and protein expression, gap junctional dye coupling and hemichannel function. We demonstrate that single and fractionated irradiation induce upregulation of proatherogenic Cx43 and downregulation of atheroprotective Cx40 gene and protein levels in a dose-dependent manner. Single and fractionated irradiation furthermore increased gap junctional communication and induced hemichannel opening. Our findings indicate alterations in Cx expression that are typically observed in endothelial cells covering atherosclerotic plaques. The observed radiation-induced increase in Cx channel function may promote bystander signaling thereby exacerbating endothelial cell damage and atherogenesis.

AB - Radiotherapy is an effective treatment for most tumor types. However, emerging evidence indicates an increased risk for atherosclerosis after ionizing radiation exposure, initiated by endothelial cell dysfunction. Interestingly, endothelial cells express connexin (Cx) proteins that are reported to exert proatherogenic as well as atheroprotective effects. Furthermore, Cxs form channels, gap junctions and hemichannels, that are involved in bystander signaling that leads to indirect radiation effects in non-exposed cells. We here aimed to investigate the consequences of endothelial cell irradiation on Cx expression and channel function. Telomerase immortalized human Coronary Artery/Microvascular Endothelial cells were exposed to single and fractionated X-rays. Several biological endpoints were investigated at different time points after exposure: Cx gene and protein expression, gap junctional dye coupling and hemichannel function. We demonstrate that single and fractionated irradiation induce upregulation of proatherogenic Cx43 and downregulation of atheroprotective Cx40 gene and protein levels in a dose-dependent manner. Single and fractionated irradiation furthermore increased gap junctional communication and induced hemichannel opening. Our findings indicate alterations in Cx expression that are typically observed in endothelial cells covering atherosclerotic plaques. The observed radiation-induced increase in Cx channel function may promote bystander signaling thereby exacerbating endothelial cell damage and atherogenesis.

KW - radiotherapy

KW - connexin

KW - dose fractionation

KW - hemichannels

KW - X-rays

KW - endothelial cells

UR - https://ecm.sckcen.be/OTCS/llisapi.dll?func=ll&objId=34770950&objaction=overview&tab=1

U2 - 10.1038/s41598-019-39317-9

DO - 10.1038/s41598-019-39317-9

M3 - Article

VL - 9

SP - 1

EP - 16

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 4643

ER -

ID: 5324923