Meow to Mars — Will Space Help or Hurt Mi’s Heart?

Sarcomere Genes in Microgravity

Overview

Can a journey to Mars actually be good for Mi’s heart? Mi is a British Shorthair, a breed particularly predisposed to hypertrophic cardiomyopathy (HCM) — the most common heart disease in cats and one that also affects 1 in 500 humans. The MYBPC3 gene mediates HCM by disrupting the cardiac myosin-binding protein C (cMyBP-C), which regulates muscle contraction in the sarcomere. On Earth, the heart must work against gravity’s hemodynamic load. In microgravity, that mechanical load disappears — but does this compensate for or compound the effects of MYBPC3 mutations?

Hypothesis

Microgravity differentially reduces MYBPC3 gene expression in mutant versus wild-type cardiomyocytes, revealing whether mechanical unloading compensates for or compounds hypertrophic cardiomyopathy in space. The molecular target is the MYBPC3 gene — two mutations associated with HCM in cats (A31P and R820W), with myriad other MYBPC3 mutations linked to HCM in humans.

Setup

Cardiomyocyte cultures carrying both wild-type and known mutant MYBPC3 variants are prepared on Earth. Identical sample sets are sent to the ISS and processed in parallel on the ground as controls. On the ISS, mRNA transcripts of MYBPC3 are amplified using the miniPCR Mini16 Thermal Cycler and detected with the P51 Molecular Fluorescence Viewer, comparing band intensity between ISS and Earth samples. The BioBits Cell-Free Protein Expression Kit is used to express cMyBP-C protein from the amplified cDNA, testing whether microgravity affects protein translation as well as transcription.

References

1. Granstrom, S. et al. (2011). Prevalence of hypertrophic cardiomyopathy in a cohort of British Shorthair cats in Denmark. J Vet Intern Med, 25(4), 866-871. doi:10.1111/j.1939-1676.2011.0751.x
2. Maron, B. J. et al. (1995). Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Circulation, 92(4), 785-789. doi:10.1161/01.CIR.92.4.785
3. Carrier, L. et al. (2015). Cardiac myosin-binding protein C (MYBPC3) in cardiac pathophysiology. Gene, 573(2), 188-197. doi:10.1016/j.gene.2015.09.008
4. Sy, M. R. et al. (2023). Cardiac function, structural, and electrical remodeling by microgravity exposure. Am J Physiol Heart Circ Physiol, 324(1), H1-H13. doi:10.1152/ajpheart.00611.2022

Data

See the proposal document and reference literature.