Epidemiological evidence has established a link between cardiovascular disease and exposure of the heart and major vessels to doses above 500mGy. At lower doses the evidence for a detrimental effect is inconclusive. In part, this is due to the lack of appropriate epidemiological studies, coupled with lack of knowledge of the processes involved that is needed for construction of mathematical models. The ProCardio consortium will study cardiovascular outcomes in childhood cancer survivors where the radiation doses given to the heart are available. These data will be interrogated using new mathematical models developed from the data from our molecular and biological studies. These will use state-of-the-art technologies to map cardiovascular changes after photon irradiation at both low doses and low dose rates. This will be complemented by comparative studies using high LET irradiation. We will apply an integrative approach to combine transcriptional (mRNA and miRNA) and translational (proteomics) studies to understand the disease processes. High throughput proteomics (ICPL, SILAC and label-free analysis) will be used to identify new biomarkers of radiation-induced cardiovascular disease for future molecular epidemiological studies. These will be validated using the archives of cardiovascular tissue samples from the Mayak facility.