THIS DESCOPED APPLICATION IS DESIGNED TO ADDRESS KEY ASPECTS OF THE RESEARCH GOALS PUT FORWARD IN TOPIC 6 OF NRA NNJ16ZSA001N-SRHHC SPACE RADIATION AND HUMAN HEALTH COUNTERMEASURES TOPICS : 1) TO PROVIDE DETAILED PHYSIOLOGICAL AND BIO-MOLECULAR CHARACTERIZATION OF RISK AND PREDICTION FOR CARDIAC DISEASE FROM MICROGRAVITY AND SPACE-LIKE RADIATION DOSES THAT ARE MISSION RELEVANT FOR FUTURE HUMAN SPACEFLIGHT BEYOND LOW EARTH ORBIT AND 2) TO DETERMINE RELATIVE BIOLOGICAL EFFECTIVENESS (RBE) VALUES FOR SPACE RADIATION IN APPROPRIATE ANIMALS USING RELEVANT INTERMEDIATE AS WELL AS LATE PHYSIOLOGICAL ENDPOINTS AND EFFECTS. THESE EXPERIMENTALLY DERIVED RBE VALUES WILL PROVIDE QUANTITATIVE INPUTS INTO METHODS AND MODELS TO CALCULATE DEGENERATIVE TISSUE RESPONSES IN HUMANS FOLLOWING EXPOSURES IN SPACE. THE PROPOSED STUDIES CENTER ON ASSESSMENT OF THE DEGENERATIVE TISSUE EFFECTS OF SPACE RADIATION ON CARDIAC DISEASE. THE CENTRAL HYPOTHESIS OF THIS PROJECT IS THAT SIMULATED WEIGHTLESSNESS INTERACTS WITH WHOLE BODY EXPOSURE TO SPACE RELEVANT DOSES OF RADIATION TO POTENTIATE RISK FOR CARDIAC DISEASE. THREE SPECIFIC AIMS ARE PROPOSED TO DIRECTLY ADDRESS THE ISSUE OF RISK FOR CARDIAC DISEASE USING EXPERIMENTAL APPROACHES IN A RAT MODEL RELEVANT TO THE RESEARCH QUESTIONS. THE PROPOSED INVESTIGATIONS DIRECTLY ADDRESS IMPORTANT ASPECTS OF THE NASA HUMAN RESEARCH PROGRAM (HRP) DEGENERATIVE TISSUE GAPS AS SET FORTH IN THE HUMAN RESEARCH ROADMAP. HRP GAPS ARE IDENTIFIED AND ADDRESSED BY EACH SPECIFIC AIM. THE PROPOSED RESEARCH WILL PROVIDE IMPORTANT INFORMATION TO HELP CLOSE THESE GAPS.