Abstract
Spaceflight and microgravity (μg) environments induce numerous cardiovascular changes that affect cardiac structure and function, and understanding these effects is essential for astronaut health and tissue engineering in space. This review compiles and analyzes over 30 years of research on the impact of real and simulated μg on cardiomyocytes. A comprehensive literature search was conducted across five databases, and 62 eligible studies involving cardiac cells under μg or spaceflight conditions were compiled and analyzed. Despite the great heterogeneity in terms of cardiac model, microgravity platform, and exposure duration, multiple studies consistently reported alterations in Ca(2+) handling, metabolism, contractility, and gene expression. Three-dimensional human-induced pluripotent stem cell-derived cardiomyocyte (HiPSC-CM) models generally showed enhanced tissue maturation and proliferation parameters, suggesting potential therapeutic benefits, while 2D models mostly exhibited stress-related dysfunction. In vivo simulated microgravity studies, such as the hindlimb unloading (HU) model, show structural and functional cardiac remodeling, and real μg studies confirmed various effects seen under the HU model in multiple rodent species. Thus, μg exposure consistently induces cardiac changes at the cellular and molecular level, while model choice, microgravity platform, and exposure duration critically influence the outcomes.