Epidemiological and animal studies increasingly recognize the detrimental effects of ionizing radiation exposure, even at low doses. These health effects not only involve the increased risk of developing cancer, but also include non-cancer effects such as cardiovascular disease. Intriguingly, long-term radiation-induced changes seem to share several similarities with ageing, defined by chronic oxidative stress, apoptosis, inflammation, and genetic instability among others. Indeed, an association between radiation exposure and ageing or premature senescence is now evidenced and becoming well documented. As age has been shown to be the dominant risk factor for atherosclerotic cardiovascular diseases, a strong interest in studying the effect of radiation on ageing of the cardiovascular system is emerging. Recently, our group in collaboration with others demonstrated premature senescence in human endothelial cells exposed to chronic low dose radiation. Follow-up studies implicated the PI3K/Akt/mTOR pathway as a potential cause of senescence, with insulin growth factors (IGFs) and IGF-binding proteins (IGFBPs) playing a key role. To further elucidate the role of this signaling cascade, we will first optimize senescence detection assays (β-Gal and CPRG assay). Next, different doses of ionizing radiation comparable to radiological and/or radiotherapeutical interventions will be tested on different human endothelial cell lines. In a last part of this thesis, the involvement of the above described signaling molecules will be tested by treatment of the cells with specific inhibitors. Finding the underlying mechanisms to explain the cardiovascular effects of ionizing radiation is essential to further improve the current radiation protection system and to develop future countermeasures for e.g. radiotherapy patients.
|State||Published - 20 Jun 2017|