Cardiovascular effects of space radiation

Astronauts on long duration missions beyond low Earth orbit will be confronted with a unique radiation environment that increases risks for adverse health effects, including cancer and cardiovascular disease. Studies in our lab in collaboration with Dr. Michael Weil at CSU seek to understand the impact of simulated space radiation exposure on cardiovascular function and disease risk, and evaluate potential countermeasures to mitigate these risks and preserve cardiovascular function during and after prolonged spaceflight.

Astronauts on long duration missions beyond low Earth orbit will be confronted with a unique radiation environment know as galactic cosmic radiation (GCR). While human exposures to deep space radiation have been limited to short duration flights in the Apollo program, accumulating evidence from both humans and experimental models suggest that more prolonged GCR exposures many increase risk for adverse health effects such as cancer and cardiovascular disease. Understanding these risks and how to mitigate them will be essential to enable deep space exploration and future human colonization of extraterrestrial environments.

In studies funded by NASA, in collaboration with Dr. Mike Weil at CSU’s Department of Environmental and Radiological Health Sciences, our lab has investigated the effect of simulated GCR on cardiovascular function in mice and rats using a custom-built irradiation facility designed and commissioned for the NASA Specialized Center of Research on Carcinogenesis. These studies revealed that prolonged exposures to low-dose 252Cf neutrons over a 200-400 days induced moderate cardiac hypertrophy and contractile dysfunction detected by serial echocardiography in both male and female mice from two different mouse strains. These impairments were associated with impaired cardiac mitochondrial function, indicated by lower respiratory capacity and greater release of reactive oxygen species. This finding is consistent with accumulating evidence indicating that mitochondria  are a primary locus of tissue injury during spaceflight, perhaps by inducing damage to mitochondria DNA.

Recently, we were funded by the Translational Research Institute for Space Health (TRISH) division of NASA to investigate the effects of simulated space radiation on human heart tissues engineered from inducible pluripotent stem cells (iPSCs) in collaboration with Dr. Joseph Wu’s group at Stanford University. Ongoing studies are evaluating the effect of protracted low-dose neutron and gamma irradiation on physiological outcomes (contractile and mitochondrial function), gene and protein expression (transcriptomics, proteomics, single cell sequencing), and biomarker discovery (secretome analyses) from these engineered heart tissues. Future studies will evaluate the effects of small molecule therapies and gene-targeting countermeasures to mitigate these effects, including use of novel protein nucleic acid technology to influence expression of multi-gene networks linked to radiation injury in collaboration with Dr. Anushree Chatterjee at UC Boulder.