Integrative proteomic and microRNA analysis of primary human coronary artery endothelial cells exposed to low-dose gamma radiation

Abstract

High doses of ionising radiation significantly increase the risk of cardiovascular disease (CVD), the vascular endothelium representing one of the main targets. Whether radiation doses lower than 500 mGy induce cardiovascular damage is controversial. The aim of this study was to investigate radiation-induced expression changes on protein and microRNA (miRNA) level in primary human coronary artery endothelial cells after a single 200 mGy radiation dose (Co-60). Using a multiplex gel-based proteomics technology (2D-DIGE), we identified 28 deregulated proteins showing more than ±1.5-fold expression change in comparison with non-exposed cells. A great majority of the proteins showed up-regulation. Bioinformatics analysis indicated "cellular assembly and organisation, cellular function and maintenance and molecular transport" as the most significant radiation-responsive network. Caspase-3, a central regulator of this network, was confirmed to be up-regulated using immunoblotting. We also analysed radiation-induced alterations in the level of six miRNAs known to play a role either in CVD or in radiation response. The expression of miR-21 and miR-146b showed significant radiation-induced deregulation. Using miRNA target prediction, three proteins found differentially expressed in this study were identified as putative candidates for miR-21 regulation. A negative correlation was observed between miR-21 levels and the predicted target proteins, desmoglein 1, phosphoglucomutase and target of Myb protein. This study shows for the first time that a low-dose exposure has a significant impact on miRNA expression that is directly related to protein expression alterations. The data presented here may facilitate the discovery of low-dose biomarkers of radiation-induced cardiovascular damage.

High and Low Doses of Ionizing Radiation Induce Different Secretome Profiles in a Human Skin Model

“…This implies that low doses of ionizing radiation likely have stimulating effects on the secretome, which is in agreement with proteomic studies of endothelial cell exposure to low dose gamma radiation (<50 cGy) [35], [36]…”

MiR‐23a Regulates the Vasculogenesis of Coronary Artery Disease by Targeting Epidermal Growth Factor Receptor

“…Mechanistically, circulating EGFR protein mobilizes EPCs by activating matrix metalloproteinase-9 (MMP-9), which cleaves membrane-bound cKit ligand to release soluble cKit ligand (also known as stem cell factor) [29,30]. This then stimulates cKit + stem cells, including EPCs, to migrate from a quiescent bone marrow niche to the vascular zone, thereby translocating the cells into a proliferative state [17]. Thus, anti-EGFR miRNAs identified in this study may contribute only in part of the reduced EPC number and activity in patients with CAD.…”

Ionizing radiation and atherosclerosis: Current knowledge and future challenges

“…Strain specific differences in low-dose radiation effects on atherosclerosis progression after exposure at early and late stage disease in knockouts (ApoE-/-). alterations, suggesting that the involvement of these small noncoding RNAs in the cellular response to ionizing radiation exposure [62]. Interestingly, recent work has shown that microRNAs can modulate the regulation of radiation-induced DNA damage and premature senescence [63].…”