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The Effects of Simulated and Real Microgravity on Vascular Smooth Muscle Cells

Christopher Ludtka
Christopher Ludtka
 oraz 
Josephine B. Allen
Josephine B. Allen
   | 25 maj 2024
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Article Category: Research Note
Data publikacji: 25 maj 2024
Zakres stron: 46 - 59
DOI: https://doi.org/10.2478/gsr-2024-0003
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© 2024 Christopher Ludtka et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Figure 1.

Experimental methods used to simulate microgravity. [A] Synthecon Rotating Wall Vessel (RWV) bioreactor. [B] SMCs on microcarrier beads in preparation for use in the RWV. [C] Gravite 3D clinostat. [D] Yuri/Airbus RPM with two independently driven perpendicular frames. [E] Illustration of hindlimb unloading for rodents; made with BioRender.
Experimental methods used to simulate microgravity. [A] Synthecon Rotating Wall Vessel (RWV) bioreactor. [B] SMCs on microcarrier beads in preparation for use in the RWV. [C] Gravite 3D clinostat. [D] Yuri/Airbus RPM with two independently driven perpendicular frames. [E] Illustration of hindlimb unloading for rodents; made with BioRender.

Figure 2.

Illustration of an artery in cross-section, and its constituent layers and components. Made with BioRender.
Illustration of an artery in cross-section, and its constituent layers and components. Made with BioRender.

Figure 3.

Illustration of microgravity control conditions. [A–C] Comparison of three normal gravity controls to assess the full range of conditions relevant to comparison with simulated microgravity culture. [D] Conditions of an experimental sample in simulated microgravity. Actual spaceflight culture does not have equivalent fluid convection to benchtop reactors. Adapted from Poon 2020.
Illustration of microgravity control conditions. [A–C] Comparison of three normal gravity controls to assess the full range of conditions relevant to comparison with simulated microgravity culture. [D] Conditions of an experimental sample in simulated microgravity. Actual spaceflight culture does not have equivalent fluid convection to benchtop reactors. Adapted from Poon 2020.

Figure 4.

(A) Phase contrast of coculture of EA.hy926 HUVEC-like cells, vascular smooth muscle cells, and fibroblasts at 21 days of RPM simulated microgravity (phase-contrast). (B, C) Sirius Red staining of cocultures of EA.hy926 HUVEC-like cells, vascular smooth muscle cells, and fibroblasts at 21 days of RPM simulated microgravity. Adapted from Grimm et al. (2014).
(A) Phase contrast of coculture of EA.hy926 HUVEC-like cells, vascular smooth muscle cells, and fibroblasts at 21 days of RPM simulated microgravity (phase-contrast). (B, C) Sirius Red staining of cocultures of EA.hy926 HUVEC-like cells, vascular smooth muscle cells, and fibroblasts at 21 days of RPM simulated microgravity. Adapted from Grimm et al. (2014).

Figure 5.

Scheme of P2 Receptor Alteration and the Postulated Paracrine Effect in ECs and SMCs under Simulated Microgravity. Expression levels of several P2 receptor were altered in ECs and SMCs under 24 h clinostat-simulated microgravity. P2X7 and P2Y2 expression was differentially altered between ECs and SMCs under simulated microgravity. The change in P2X7 expression in ECs was compensated under SMC-conditioned medium and vice versa. Adapted from Zhang et al. 2014.
Scheme of P2 Receptor Alteration and the Postulated Paracrine Effect in ECs and SMCs under Simulated Microgravity. Expression levels of several P2 receptor were altered in ECs and SMCs under 24 h clinostat-simulated microgravity. P2X7 and P2Y2 expression was differentially altered between ECs and SMCs under simulated microgravity. The change in P2X7 expression in ECs was compensated under SMC-conditioned medium and vice versa. Adapted from Zhang et al. 2014.

Summary of VSMC microgravity literature sorted by experimental platform used.

Experiment Platform Paper Cell Type Time in μG Results of Microgravity In Vivo or In Vitro Reporting of Sample Sex
Clinorotation (simulated μg) Zhang 2014 Bovine aortic VSMC 12 d Alters P2 receptor expression pattern; VSMCs secreted different cytokines under μg, leading to increased (pathogenic) proliferation and migration In Vitro Not specified
Kang 2013 Rat aortic VSMC 24 - 144 h Decreased proliferation and migration, increased cell apoptosis and NO release, and disrupted cytoskeleton; ≥72 h of μg caused contractile phenotype via sm-MHC upregulation Male Only
Kang 2013 Rat aortic VSMC 4 d; 6 d Cell surface HSPG reduced; NOS activated; downregulation of glypican-1, constitutive NOS, and F-actin; Heparinase III and NaClO3 attenuated NOS and F-actin changes Male Only
Random position machine (simulated μg) Grimm 2014 Vascular SMC 21 d VSMCs in coculture with EA.hy926 cells and fibroblasts can form tubular structures in vitro In Vitro Not Specified
Hindlimb unloading (simulated μg) Jiang 2022 Rat cerebral artery VSMC 28 d Induced phenotype switching and proliferation, which could be mitigated by propyl pyrazole triol activation of ERα signaling to reestablish fission-fusion-mitophagy hemostasis In Vivo Male Only
Liu 2021 Rat cerebral artery VSMC 3 w Increased cytoplasmic Ca2+; decreased mitochondrial/sarcoplasmic reticulum Ca2+; fusion proteins (mitofusin 1/2 [MFN1/2]) downregulated and fission proteins (dynamin-related protein 1 [DRP1] and fission-mitochondrial 1 [FIS1]) upregulated Male Only
Zhang 2020 Rat cerebral artery VSMC 28 d Increased proliferation and migration, modulated by T-type CaV 3.1 channel's regulation of calcineurin/NFATc3 pathway Not Specified
Zhang 2020 Rat cerebral artery VSMC 7 - 28 d Mitochondria oxidative stress & ER stress caused phenotypic shifts in VSMCs via PERK-elFα2-ATF4 and PI3K/Akt/mTOR pathways; mitoTEMPO helped alleviate these effects Male Only
Hindlimb unloading (simulated μg) Su 2020 Rat cerebral and mesenteric artery VSMC 4 w Increased proliferation and reduced apoptosis, acid sphingomyelinase protein, and ceramide content in cerebral artery SMCs; opposite effect in mesenteric artery SMCs In Vivo Male Only
Kang 2019 Rat common carotid artery, abdominal aorta, and femoral artery VSMC 3 w For VSMCs & ECs: all NOS isoforms downregulated in aorta, iNOS and eNOS upregulated in carotid artery; VSMC apoptosis reduced in aorta and carotid In Vivo Female Only
Jiang 2018 Rat basilar and femoral artery VSMC 4 w VSMC volume, arterial wall thickness, and p-FAK Y397 and p-Src Y418 expression increased in basilar artery, decreased in femoral artery Male Only
Ghosh 2016 Mouse skeletal muscle artery VSMC 13 - 16 d Reduced vasodilatory response to exogenous NO; reduction increased by radiation exposure Male Only
Dabertrand 2012 Rat hepatic portal vein VSMC 8 d Decreased expression in ryanodine receptor subtype 1; calcium signaling pathway adaptation to pressure via regulation of ryanodine receptor subtype 1 expression Male Only
Xue 2011 Rat cerebral and mesenteric artery VSMC 28 d Increased sarcoplasmic reticulum CaL channel and ryanodine-sensitive Ca2+ release functions in cerebral SMCs; decreased in mesenteric VSMCs Male Only
Xue 2007 Rat cerebral and mesenteric artery VSMC 3 d; 28 d Increased L-type Ca2+ channel density and protein expression in cerebral artery VSMCs; decreased channel density and protein expression in mesenteric artery VSMCs Male Only
Coinu 2006 Rat aortic VSMC 24 h Induced partial arrest in cell cycle (at G2M) and increased expression of p14-3-3, HSP70, HSP60 and p21 Male Only
Morel 1997 Rat portal vein VSMC 14 d Ca2+ sensitivity of ryanodine-sensitive Ca2+ release channels was unchanged by μg; Ca2+ waves were significantly reduced and [3H]ryanodine binding to vascular membranes was inhibited Male Only
Spaceflight (real μg) Scotti 2024 Human aortic VSMC 3 d Down-regulation of markers of contractile, synthetic, and osteogenic phenotypes, including α-SMA, matrix metalloproteinases, and bone morphogenic proteins In Vitro Not Specified
Sofronova 2015 Mouse basilar artery 30 d Reduced vasoconstriction via voltage-gated Ca2+ and thromboxane A2 receptors in cerebral arteries In Vivo Male Only
Behnke 2013 Mouse mesenteric artery 13 d; 15 d Reduced maximum vasoconstriction response to norepinephrin, KCl, and caffeine immediately after and 1-day post-spaceflight; downregulated arterial ryanodine receptor-3 mRNA expression In Vivo Female Only
Dabertrand 2012 Rat hepatic portal vein VSMC 8 d Decreased expression in ryanodine receptor subtype 1; calcium signaling pathway adaptation to pressure via regulation of ryanodine receptor subtype 1 expression Both Male Only
eISSN:
2332-7774
Język:
Angielski
Częstotliwość wydawania:
2 razy w roku
Dziedziny czasopisma:
Life Sciences, other, Materials Sciences, Physics
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