Epidemiological studies on acutely and chronically exposed individuals indicate that ionising radiation could be a risk factor for cardiovascular diseases. Experimental data regarding radiation-induced cardiovascular late effects are limited and biological mechanisms behind these late effects are still unclear. The estimation of risks concerning low-dose rate and low-dose ionising radiation is still challenging due to lack of experimental evidence.

The first paper of the thesis describes the radiation-induced protein alterations in cardiac tissue of total body irradiated mice. We use a label-free proteomic approach to identify altered proteins from formalin-fixed paraffin-embedded heart tissue. Comparison between the cardiac proteomes of control and irradiated mice indicates the respiratory chain, lipid metabolism and pyruvate metabolism pathways are affected. We suggest that these biological processes may play a vital role in radiation-induced cardiovascular diseases.

In the second paper (manuscript) we hypothesized that chronic low-dose rate ionising radiation accelerates premature senescence in endothelial cells and that this may contribute to the radiation-induced cardiovascular diseases. We tested our hypothesis by systematically analysing the growth rate, the number of accumulated senescent cells and the protein expression profiles of the chronically exposed primary human umbilical vein endothelial cells until the cells entered senescence. Decrease in cumulative population doublings and increase in senescent-associated beta-galactosidase stained cells show that chronic exposure to radiation accelerates endothelial cells senescence. Our proteomic results suggest that the cytoskeletal organisation, cell-cell communication and adhesion, inflammation and carbohydrate metabolism were influenced by chronic exposure to radiation. A few deregulated proteins have previously been associated with replicative and stress-induced premature senescence. The results presented here provide new insights on radiation-induced premature senescence in endothelial cells and the changes in protein expression associated with this process.