Endothelial dysfunction markers and immune response indices in cosmonauts’ blood after long-duration space flights

Abstract

Space flight factors are known to cause a malfunction in the human immune system and lead to damage to blood vessels. The hemostatic function of endothelium during space missions and its interaction with human immunity has not been determined so far. In this work, we investigated the markers of endothelial activation and damage (plasma concentrations of soluble thrombomodulin fraction (sTM), von Willebrand factor (vWF), highly sensitive C-reactive protein (hs-CRP)), as well as the level of D-dimer and compared them to the immunological parameters characterizing the state of human humoral and cellular immunity. The immune status of long-duration ISS crewmembers was assessed by whole-blood testing, and comprehensive postflight immune assessment included the analysis of leukocyte distribution. Flow cytometry was applied to determine the absolute counts and the percentage of lymphocyte subsets: B cells (CD19+), T cells (CD3+, CD3+CD4+, CD3+CD8+), NK cells (CD3−CD16+CD56+, CD11b+CD56+), and activated subsets (CD3+CD25+ and CD3+HLA-DR+). The in vitro basal cytokine production was investigated in whole blood cell culture. The cytokines IFN-gamma, IL-1-beta, IL-4, IL-6, IL-10, IL-18, and TNF-alpha were measured in plasma and the 24-h supernatants by a sensitive enzyme-linked immunosorbent assay. A significant increase in the plasma levels of vWF and hs-CRP and a decrease in the concentration of sTM after spaceflights were detected. Divergent changes in the parameters characterizing the state of the immune system were observed. We propose that the changes revealed may lead to an increase in the procoagulant activity of blood plasma, suppression of protein C activation and thrombin inhibition, as well as to an increase in the adhesive-aggregate potential of platelets, especially in case of changes in the rheological characteristics of blood flow during re-adaptation to ground conditions. We also speculate that the immune system might play an important role in vessel damage during long-duration missions.

Biomimetic Nanoparticle-Mediated Target Delivery of Hypoxia-Responsive Plasmid of Angiotensin-Converting Enzyme 2 to Reverse Hypoxic Pulmonary Hypertension

“…Hypoxia-induced release of reactive oxygen species results in endothelial injury, collagen exposure, and the high expression of vWF in pulmonary vascular endothelium. 31,32 GPIbα and GPVI on the platelet membrane can, respectively, bind to vWF and the exposed collagen and promote platelets to adhere to the damaged endothelial surface. 33,34 Besides, the selfrecognition receptor CD47 on the platelet membrane can prevent nanoparticles from phagocytosis by macrophages; 28 therefore, a platelet bionic drug delivery system can prolong E,F) MTT assay and immunofluorescence staining of α-SMA and Ki67 (red, α-SMA; green, Ki67; blue, DAPI to stain the nuclei) to represent the inhibition effects on the hypoxia proliferation of PASMCs after treatment with ACE2-CS-PRT@PM, ACE2-CS-PRT, Fc-CS-PRT@PM, or transfection with HTSFcACE2 plasmid or HTSFc plasmid by using Lipofectamine 2000 reagent.…”

“…Platelet membranes are rich in membrane proteins including CD47, GPIbα, and GPVI. Hypoxia-induced release of reactive oxygen species results in endothelial injury, collagen exposure, and the high expression of vWF in pulmonary vascular endothelium. , GPIbα and GPVI on the platelet membrane can, respectively, bind to vWF and the exposed collagen and promote platelets to adhere to the damaged endothelial surface. , Besides, the self-recognition receptor CD47 on the platelet membrane can prevent nanoparticles from phagocytosis by macrophages; therefore, a platelet bionic drug delivery system can prolong the circulation time of drugs in the body. , ACE2-CS-PRT@PM probably selectively distributes in hypoxia-injured pulmonary vascular endothelium and has a slowdown clearance.…”

Preliminary evidence of high prevalence of cerebral microbleeds in astronauts with spaceflight experience

“…Microgravity produces a cephalic fluid shift, diminished postflight orthostatic tolerance, cardiac arrhythmias ( Anzai et al, 2014 ), arterial stiffening ( Hughson et al, 2016 ), and potentially increases in intracranial pressure ( Lawley et al, 2017 ), among other effects ( Demontis et al, 2017 ). Increased exposure to ionizing radiation has also been shown to increase the risk of cardiovascular disease, by exacerbating atherosclerotic processes ( Koutroumpakis et al, 2022 ), producing structural damage to blood vessels ( Kuzichkin et al, 2022 ) and exacerbating microgravity-related thrombosis risks ( Marshall-Goebel et al, 2019 ).…”