Space travel alters human vascular cell function, study finds

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In a recent study published in NPJ Microgravity, scientists explore the impact of spaceflight on human vascular smooth muscle cells at the transcriptomic level.

Study: Spaceflight effects on human vascular smooth muscle cell phenotype and function. Image Credit: Cinefootage Visuals / Shutterstock.com

Study: Spaceflight effects on human vascular smooth muscle cell phenotype and function. Image Credit: Cinefootage Visuals / Shutterstock.com

Background

Astronauts traveling in spaceflight are exposed to a highly hostile environment characterized by microgravity, high-level radiation, and many other foreign factors. Taken together, these factors induce a wide range of physiological changes, especially at the cellular level.

More specifically, human exposure to microgravity can cause muscular atrophy, bone resorption, flattening of the eye, and cardiovascular deconditioning. The latter is characterized by loss of vascular tone, reduced total blood volume, and diminished cardiac output, and it can lead to severe health complications in astronauts.

In the current study, scientists explore cardiovascular deconditioning-associated behavioral changes at the cellular level. To this end, human vascular smooth muscle cells cultured in microgravity and aboard the International Space Station (ISS) were subjected to a transcriptomic analysis to determine the mechanisms involved in potential pathway regulation.

Important findings

Compared to control cells, which remained at the ground level, spaceflight vascular smooth muscle cells exhibited differential expression of over 4,422 genes, 43% of which were upregulated and 57% downregulated.

The pathway analysis of transcriptomic data identified 28 pathways that were significantly inhibited. Comparatively, the phosphatase and tensin homolog (PTEN) signaling and peroxisome proliferator-activated receptor α (PPARα)/retinoid X receptor α (RXRα) pathways were significantly activated.

Three networks associated with differentially expressed genes were identified and corresponded to cardiovascular disease, as well as cardiovascular system development and function.

Spaceflight also strongly affected several components of the signal transducer and activator of transcription 3 (STAT3), nuclear factor κB (NF-κB), phosphoinositide 3 kinase (PI3K)/AKT, hypoxia-inducible factor 1 α (HIF1α), and endothelin-1 pathways.

A total of 22 cardiovascular signaling pathways were also identified, three of which were significantly inhibited. These pathways were involved in cardiac hypertrophy signaling, the role of nuclear factor of activated T-cells (NFAT) in cardiac hypertrophy, and cardiac hypertrophy signaling.

Gene ontology (GO) analysis of significantly affected differentially expressed genes was also performed. Moreover, GO annotations were divided into three parent terms of biological process, cellular component, and molecular function.

Most of the differentially expressed genes were associated with extracellular processes and extracellular matrix interaction terms. Extracellular region and space were the most represented cellular component terms. Molecular function included several binding terms, such as heparin, extracellular matrix, and glycosaminoglycan binding, as well as extracellular matrix structural constituent.

The analysis of cellular component and molecular function terms revealed significant changes in extracellular matrix genes related to both production and cellular adherence. The analysis of biological process terms showed enrichment of cell, cell-cell, and homophilic cell adhesion. 

These findings collectively indicate significant changes in extracellular matrix function and binding, as well as cellular processes related to proliferation, migration, and angiogenesis in spaceflight-exposed vascular smooth muscle cells.

Further analysis revealed that upregulated genes were associated with cell division-related processes and components. Comparatively, downregulated genes were associated with cellular adhesion, signal transduction, and various binding functions, including protein, calcium ion, heparin, and integrin binding.

Significantly altered expression of genes related to vascular smooth muscle cell contraction, synthetic and osteogenic phenotypes were observed during spaceflight. Most of the components related to these phenotypes, including smooth muscle alpha-actin (αSMA), matrix metalloproteinases (MMPs), and bone morphogenic proteins (BMPs), were downregulated in vascular smooth muscle cells exposed to spaceflight.

Study significance

The current study reports a reduction in the contractile phenotype of vascular smooth muscle cells exposed to spaceflight. These cells also appear to undergo a phenotype switching towards a synthetic or osteogenic phenotype. Additionally, the downregulated expression of most of the identified genes indicates that spaceflight exposure causes broad transcriptional inhibition in vascular smooth muscle cells.

Given the unaltered functioning of certain cellular processes during a 72-hour spaceflight, the scientists hypothesize that vascular smooth muscle cells may adapt to microgravity when exposed to the space environment for more than 72 hours. However, genetic changes may collectively lead to an alteration in vascular smooth muscle cell functions.

Future studies are needed to determine the specific mechanisms by which cells alter their behavior in response to spaceflight.  

Journal reference:
  • Scotti, M. M., Wilson, B. K., Bubenik, J. L., et al. (2024). Spaceflight effects on human vascular smooth muscle cell phenotype and function. NPJ Microgravity 10(41). doi:10.1038/s41526-024-00380-w/
Dr. Sanchari Sinha Dutta

Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.

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