In a recent study published in NPJ microgravity, Scientists are investigating the effects of spaceflight on human vascular smooth muscle cells at the transcriptomic level.

study: Effects of spaceflight on human vascular smooth muscle cell phenotype and function. Image credit: Cinefootage Visuals / Shutterstock.com

background

Astronauts during spaceflight are exposed to an extremely harsh environment characterized by microgravity, high levels of radiation, and many other external factors. Together, these factors cause a wide range of physiological changes, especially at the cellular level.

More specifically, human exposure to microgravity can cause muscle atrophy, bone resorption, eye flattening, and worsening cardiovascular conditions. The latter is characterized by a loss of vascular tone, a decrease in total blood volume, and a decrease in cardiac output, which can lead to serious health complications in astronauts.

In current research, scientists are investigating behavioral changes associated with abnormal cardiovascular conditions at the cellular level. To this end, transcriptome analysis of human vascular smooth muscle cells cultured in microgravity and on the International Space Station (ISS) was performed to uncover mechanisms involved in potential pathway regulation. I did.

important discovery

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

Pathway analysis of transcriptome data identified 28 significantly inhibited pathways. In comparison, 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, which corresponded to cardiovascular diseases, cardiovascular system development and function.

Spaceflight also disrupts signal transducer and activator of transcription 3 (STAT3), nuclear factor-κB (NF-κB), phosphoinositide 3-kinase (PI3K)/AKT, hypoxia-inducible factor 1α (HIF1α), and some endothelins. had a strong influence on the components of 1 aisle.

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

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

Most of the differentially expressed genes were related to extracellular processes and extracellular matrix interaction terms. Extracellular region and space were the most representative cellular organization terms. Molecular functions include the structural components of the extracellular matrix as well as several bonding terms such as heparin, extracellular matrix, and glycosaminoglycan linkages.

Analysis of cellular components and molecular function terms revealed significant changes in extracellular matrix genes related to both production and cell adhesion. Analysis of biological process terms showed enhanced cell, cell-cell, and homophilic cell adhesion.

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

Further analysis revealed that the upregulated genes were associated with processes and components related to cell division. In comparison, the downregulated genes were related to cell adhesion, signal transduction, and various binding functions such as protein, calcium ion, heparin, and integrin binding.

During spaceflight, significant changes in the expression of genes associated with contractile, synthetic and osteogenic phenotypes of vascular smooth muscle cells were observed. Most of the components associated with these phenotypes, such as smooth muscle alpha-actin (αSMA), matrix metalloproteinases (MMPs), and bone morphogenetic proteins (BMPs), are downregulated in vascular smooth muscle cells exposed to spaceflight. It had been.

Significance of research

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 phenotypic switch to a synthetic or osteogenic phenotype. Furthermore, the expression of most of the identified genes was downregulated, indicating that spaceflight exposure causes widespread transcriptional inhibition in vascular smooth muscle cells.

Considering that the function of certain cellular processes did not change during a 72-hour spaceflight, scientists believe that it is possible that vascular smooth muscle cells adapt to microgravity if exposed to the space environment for more than 72 hours. We hypothesize that there is a sex. However, genetic changes can collectively cause changes in vascular smooth muscle cell function.

Future research is needed to elucidate the specific mechanisms by which cells change their behavior in response to spaceflight.