Cardiovascular Remodeling in Spaceflight: Mechanotransduction, Space Radiation, and Countermeasure Strategies

Protecting cardiovascular function during longer missions beyond low Earth orbit requires understanding how altered loading and radiation affect the heart and vasculature. Evidence spans astronaut physiology and experimental models, but the links between molecular responses, tissue remodeling and functional impairment remain incompletely resolved. This narrative review integrates human observations, unloading analogs, real-flight experiments and mechanistic studies to distinguish exposure-related responses from demonstrated cardiovascular remodeling and to assess their relevance to countermeasures. Human studies show reduced cardiac work with preserved structure under studied countermeasure regimens, variable recovery across endpoints and no persistent vascular abnormalities in a small long-term cohort. Experimental systems identify endothelial, vascular smooth muscle, and matrix mechanisms that can be tested against these physiological observations, although the contributions of these mechanisms to astronaut outcomes remain uncertain. For exploration beyond low Earth orbit, combined radiation-unloading studies further show that cardiovascular effects depend on the model, endpoint and recovery interval, limiting predictions from either stressor alone. Countermeasure studies likewise show that preserved fitness can coexist with impaired orthostatic tolerance. Together, these findings support the assessment of cardiovascular risk and protection through specific functional trajectories rather than molecular changes alone. Progress requires longitudinal human phenotyping, factorial exposure studies, and mechanistic perturbation in calibrated human tissue models, with countermeasure efficacy evaluated against the functions that missions require crews to maintain.