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

Gravitational and Space Research
Volume 12 (2024): Issue 1 (January 2024)
By:
Open Access
|May 2024

Figures & Tables

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 PlatformPaperCell TypeTime in μGResults of MicrogravityIn Vivo or In VitroReporting of Sample Sex
Clinorotation (simulated μg)Zhang 2014Bovine aortic VSMC12 dAlters P2 receptor expression pattern; VSMCs secreted different cytokines under μg, leading to increased (pathogenic) proliferation and migrationIn VitroNot specified
Kang 2013Rat aortic VSMC24 - 144 hDecreased proliferation and migration, increased cell apoptosis and NO release, and disrupted cytoskeleton; ≥72 h of μg caused contractile phenotype via sm-MHC upregulationMale Only
Kang 2013Rat aortic VSMC4 d; 6 dCell surface HSPG reduced; NOS activated; downregulation of glypican-1, constitutive NOS, and F-actin; Heparinase III and NaClO3 attenuated NOS and F-actin changesMale Only
Random position machine (simulated μg)Grimm 2014Vascular SMC21 dVSMCs in coculture with EA.hy926 cells and fibroblasts can form tubular structures in vitroIn VitroNot Specified
Hindlimb unloading (simulated μg)Jiang 2022Rat cerebral artery VSMC28 dInduced phenotype switching and proliferation, which could be mitigated by propyl pyrazole triol activation of ERα signaling to reestablish fission-fusion-mitophagy hemostasisIn VivoMale Only
Liu 2021Rat cerebral artery VSMC3 wIncreased 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]) upregulatedMale Only
Zhang 2020Rat cerebral artery VSMC28 dIncreased proliferation and migration, modulated by T-type CaV 3.1 channel's regulation of calcineurin/NFATc3 pathwayNot Specified
Zhang 2020Rat cerebral artery VSMC7 - 28 dMitochondria oxidative stress & ER stress caused phenotypic shifts in VSMCs via PERK-elFα2-ATF4 and PI3K/Akt/mTOR pathways; mitoTEMPO helped alleviate these effectsMale Only
Hindlimb unloading (simulated μg)Su 2020Rat cerebral and mesenteric artery VSMC4 wIncreased proliferation and reduced apoptosis, acid sphingomyelinase protein, and ceramide content in cerebral artery SMCs; opposite effect in mesenteric artery SMCsIn VivoMale Only
Kang 2019Rat common carotid artery, abdominal aorta, and femoral artery VSMC3 wFor VSMCs & ECs: all NOS isoforms downregulated in aorta, iNOS and eNOS upregulated in carotid artery; VSMC apoptosis reduced in aorta and carotidIn VivoFemale Only
Jiang 2018Rat basilar and femoral artery VSMC4 wVSMC volume, arterial wall thickness, and p-FAK Y397 and p-Src Y418 expression increased in basilar artery, decreased in femoral arteryMale Only
Ghosh 2016Mouse skeletal muscle artery VSMC13 - 16 dReduced vasodilatory response to exogenous NO; reduction increased by radiation exposureMale Only
Dabertrand 2012Rat hepatic portal vein VSMC8 dDecreased expression in ryanodine receptor subtype 1; calcium signaling pathway adaptation to pressure via regulation of ryanodine receptor subtype 1 expressionMale Only
Xue 2011Rat cerebral and mesenteric artery VSMC28 dIncreased sarcoplasmic reticulum CaL channel and ryanodine-sensitive Ca2+ release functions in cerebral SMCs; decreased in mesenteric VSMCsMale Only
Xue 2007Rat cerebral and mesenteric artery VSMC3 d; 28 dIncreased L-type Ca2+ channel density and protein expression in cerebral artery VSMCs; decreased channel density and protein expression in mesenteric artery VSMCsMale Only
Coinu 2006Rat aortic VSMC24 hInduced partial arrest in cell cycle (at G2M) and increased expression of p14-3-3, HSP70, HSP60 and p21Male Only
Morel 1997Rat portal vein VSMC14 dCa2+ sensitivity of ryanodine-sensitive Ca2+ release channels was unchanged by μg; Ca2+ waves were significantly reduced and [3H]ryanodine binding to vascular membranes was inhibitedMale Only
Spaceflight (real μg)Scotti 2024Human aortic VSMC3 dDown-regulation of markers of contractile, synthetic, and osteogenic phenotypes, including α-SMA, matrix metalloproteinases, and bone morphogenic proteinsIn VitroNot Specified
Sofronova 2015Mouse basilar artery30 dReduced vasoconstriction via voltage-gated Ca2+ and thromboxane A2 receptors in cerebral arteriesIn VivoMale Only
Behnke 2013Mouse mesenteric artery13 d; 15 dReduced maximum vasoconstriction response to norepinephrin, KCl, and caffeine immediately after and 1-day post-spaceflight; downregulated arterial ryanodine receptor-3 mRNA expressionIn VivoFemale Only
Dabertrand 2012Rat hepatic portal vein VSMC8 dDecreased expression in ryanodine receptor subtype 1; calcium signaling pathway adaptation to pressure via regulation of ryanodine receptor subtype 1 expressionBothMale Only
DOI: https://doi.org/10.2478/gsr-2024-0003 | Journal eISSN: 2332-7774
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Language: English
Page range: 46 - 59
Published on: May 25, 2024
Published by: American Society for Gravitational and Space Research
In partnership with: Paradigm Publishing Services
Publication frequency: 2 times per year
Keywords:
spaceflight,
simulated microgravity,
smooth muscle cell,
tissue engineering,
radiation
Related subjects:
Life sciences,
Life sciences, other,
Materials sciences,
Materials sciences, other,
Physics,
Physics, other

© 2024 Christopher Ludtka, Josephine B. Allen, published by American Society for Gravitational and Space Research
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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