WE ANTICIPATE THAT THE RESULTS OF OUR PROPOSED WORK MAY BE BENEFICIAL FOR HUMAN SPACE EXPLORATION AND COULD (1) DETERMINE SINGLE, LOW-DOSE 1H, 56FE AND MIXED FIELD DOSE-RESPONSES, RADIO-BIOLOGICALLY EFFECTIVE IR THRESHOLDS IN THE HEART AND CARDIAC VASCULATURE AND WHETHER GENDER DIFFERENCES COULD MODIFY RADIO-BIOLOGICALLY EFFECTIVE IR THRESHOLDS FOR CV RISK ESTIMATES; 2) DETERMINE WHETHER SPACE RADIATION LEADS TO MODIFICATIONS IN THE CIRCULATING EXOSOMAL CARGO CONTENTS AND WHETHER IR-INDUCED EXOSOMAL CARGO MODULATIONS ARE REFLECTIVE OF SUBCLINICAL CHANGES IN THE CELLS AND ORGANS OF ORIGIN; 3) ASCERTAIN IF MODULATIONS OF EXOSOMAL CARGO MAY BE REPRESENTATIVE OF CHRONIC OXIDATIVE STRESS AND INFLAMMATION AND COULD SERVE AS EARLY BIOMARKERS OF IR-INDUCED CV DISEASE INITIATION AND PROGRESSION; 4) INTEGRATE PHYSIOLOGICAL CV ENDPOINT DATA SETS WITH GENE EXPRESSION AND EPIGENETIC DATA TO IDENTIFY BIO-MARKERS IN BIO-FLUIDS THAT COULD BE USED FOR PREDICTION OF ASYMPTOMATIC CV DISEASE IN THE SETTING OF SPACE IR, WHICH WILL INCLUDE KNOWN EARLY AND INTERMEDIATE BIO-MARKERS OF CARDIAC DAMAGE, INFLAMMATION AND OXIDATIVE STRESS, AS WELL AS CURRENTLY UNKNOWN NOVEL RADIATION-ASSOCIATED CARDIAC BIO-MARKERS.