The molecular mechanisms driving physiological changes after long duration space flights revealed by quantitative analysis of human blood proteins

Abstract

BackgroundThe conditions of space flight have a significant effect on the physiological processes in the human body, yet the molecular mechanisms driving physiological changes remain unknown.MethodsBlood samples of 18 Russian cosmonauts who had conducted long-duration missions to the International Space Station were collected 30 days before launch and on the first and seventh days after landing.ResultsA panel of 125 proteins in the blood plasma was quantitated by a well-established and highly regarded targeted mass spectrometry approach. This method involves the monitoring of multiple reactions in conjunction with stable isotope-labeled standards at the University of Victoria - Genome BC Proteomics Centre.ConclusionsReduction of circulating plasma volume during space flight and activation of fluid retention at the final stage of the flight affect the changes in plasma protein concentrations present in the first days after landing. Using an ANOVA approach, it was revealed that only 1 protein (S100A9) reliably responded to space flight conditions. This protein plays an important role in the functioning of the endothelium and can serve as a marker for activation of inflammatory reactions. Concentrations of the proteins of complement, coagulation cascades, and acute phase reactants increase in the blood of cosmonauts as measured the first day after landing. Most of these proteins’ concentrations continue to increase by the 7th day after space flight. Similar dynamics are observed for proteases and their inhibitors. Thus, there is a shift in proteolytic blood systems, which is necessary for the restoration of muscle tissue and maintenance of oncotic homeostasis.Electronic supplementary materialThe online version of this article (10.1186/s12920-019-0490-y) contains supplementary material, which is available to authorized users.

Managing Hemostasis in Space

“…20 Functionally, these cardiovascular changes are associated with significant cardiovascular deconditioning as reflected by reduced maximal oxygen uptake in astronauts returning to Earth after long-duration spaceflight. 21 Further evidence for direct vascular injury during spaceflight was suggested by Kashirina et al, 22 who found that the myeloid-related protein-14 (S100A9), a member of the S100 family of proteins that regulates myeloid cell function and inflammation, was reliably elevated after exposure to space flight. S100A9 plays an important role in augmenting vascular inflammation, where genetic knockouts have identified a specific role in recruiting leukocytes to sites of vascular injury.…”

“…Kashirina et al 22 used targeted mass spectrometry to study the effects long-duration missions to the ISS on 125 blood proteins from 18 cosmonauts. Proteins involved in coagulation (factor XI, fibrinogen, fibrinopeptide A, and the serpin plasminogen activator inhibitor-3) and acute phase reactions (haptoglobin) were increased on the first day after spaceflight.…”

“…Further examination of the cellular mechanisms involved found that changes in calcium transport and the actin cytoskeleton of platelets play a role in their response to altered gravity conditions. 40 Kashirina et al 22 used targeted mass spectrometry to study the effects long-duration missions to the ISS on 125 blood proteins from 18 cosmonauts. Proteins involved in coagulation (factor XI, fibrinogen, fibrinopeptide A, and the serpin plasminogen activator inhibitor-3) and acute phase reactions (haptoglobin) were increased on the first day after spaceflight.…”

Collection of Biospecimens from the Inspiration4 Mission Establishes the Standards for the Space Omics and Medical Atlas (SOMA)

“…There were a few instances were CPT tubes shattered in the centrifuge and plasma could not be salvaged. Plasma can be used to validate or refute previous studies, including cytokine panel 10,26 , exosomal RNA-seq 25,32 , extracellular vesicle microRNA 30 , and proteomic 20,[27][28][29] results. PBMCs were also collected, aliquoted into 6 cryovials per CPT, and stored in liquid nitrogen after slowly cooled in a Mr. Frosty to -80°C.…”

Human Adaptation to Deep Space Environment: An Evolutionary Perspective of the Foreseen Interplanetary Exploration

“…The goal is to assess the impact of these changes on health and consequently, on the safety and survival of the crew members. It is well-known that microgravity leads to a myriad of body alterations including bone and muscle mass loss, cardiovascular deconditioning, impaired exercise capacity, immune-deficiency, and alterations of peripheral metabolism (6)(7)(8). To prevent the development of these physiological modifications during spaceflights, international space agencies have put a lot of effort into the development of countermeasures.…”