Table 4.
Changes in gene regulation of endothelial cells exposed to microgravity conditions.
| Cell Type | Gene Regulation | Microgravity | Reference |
|---|---|---|---|
| Human microvascular endothelial cell line HMEC-1 |
Differentially regulated Hallmark collection gene sets: Up: HALLMARK_ADIPOGENESIS, HALLMARK_ ALLOGRAFT_REJECTION, HALLMARK_ ANDROGEN_RESPONSE, HALLMARK_BILE_ACID_ METABOLISM, HALLMARK_CHOLESTEROL_ HOMEOSTASIS, HALLMARK_COAGULATION, HALLMARK_E2F_TARGETS, HALLMARK_FATTY_ACID_METABOLISM, HALLMARK_G2M_CHECKPOINT, HALLMARK_ MITOTIC_SPINDLE, HALLMARK_MTORC1_SIGNALING, HALLMARK_MYC_TARGETS_V1, HALLMARK_ OXIDATIVE_PHOSPHORYLATION, HALLMARK_ PEROXISOME, HALLMARK_PI3K_AKT_MTOR_ SIGNALING, HALLMARK_PROTEIN_SECRETION, HALLMARK_REACTIVE_OXIGEN_SPECIES_PATHWAY, HALLMARK_SPERMATOGENESIS, HALLMARK_UV_ RESPONSE_DN Down: HALLMARK_ESTROGEN_RESPONSE_EARLY, HALLMARK_ESTROGEN_RESPONSE_LATE, HALLMARK_HEDGEHOG_SIGNALING, HALLMARK_HYPOXIA, HALLMARK_IL2_STAT5_ SIGNALING, HALLMARK_KRAS_SIGNALING_DN, HALLMARK_MYOGENESIS, HALLMARK_NOTCH_ SIGNALING, HALLMARK_P53_PATHWAY, HALLMARK_TNFA_SIGNALING_VIA_NFKB, HALLMARK_UV_RESPONSE_UP, HALLMARK_WNT_BETA_CATENIN_SIGNALING |
r-µg on the ISS for 160 h | [108] |
| HUVECs | 585 genes significantly upregulated (top 5: TXNIP, MIR15A, ANAPC1, TP53INP1, ID1); 438 genes significantly downregulated (top 5: HSPA1A and -B, HSP90AA2, ATF3, CLCA2, RYBP) | r-µg on the ISS for 10 d | [109] |
| HUVECs | Early upregulation of HSPA1A only after 4 days, string upregulation of TXNIP after 10 days | s-µg on the RWV for 4 and 10 d | [110] |
| HUVECs | Downregulation of SLCO2A1 | s-µg on a clinostat for 7 d | [111] |
| HUVECs | No significant difference in TP53 gene expression | s-µg on a clinostat for 24, 48, and 73 h | [112] |
| HUVECs | Upregulated miRNAs: hsa-miR-628-3p, hsa-miR-3195, hsa-miR-3687, hsa-miR-1257, hsa-miR-3614-5p | s-µg on a clinostat for 48 h | [113] |
| HUVECs | Upregulation of miR-22 after 72 h, concurrent downregulation of SRF and LAMC1 | s-µg on a HARV for 48, 72 and 96 h | [114] |
| HUVECs | 1870 differentially expressed miRNAs; hsa-mir-496, hsa-mir-151a, hsa-miR-296-3p, hsa-mir-148a, hsa-miR-365b-5p, hsamiR-3687, hsa-mir-454, hsa-miR-155-5p, and hsa-miR-145-5p involved in cell adhesion, angiogenesis, cell cycle, JAK-STAT signaling, MAPK signaling, nitric oxide signaling, VEGF signaling, and wound healing pathways | s-µg on a 3D-clinostat for 2 h | [115] |
| Human CVECs | Upregulation of BAX, CASP3, and CYP2D6 after 1 and 3 days Downregulation of BCL2 after 1 and 3 days |
s-µg on an RCCS for 1 and 3 d | [116] |
| EA.hy926 | Upregulation of CXCL8 and FN1 in spheroids | s-µg on an RPM for 35 d | [117] |
| EA.hy926 | Differential regulation of TIMP1, IL6, CXCL8, CCL2, B2M | r-µg on the ISS for 12 d | [118] |
| EA.hy926 | Top 20 upregulated genes in EA.hy926 exosomes: ACTB, PGK1, HSPA8, RPL7A, FTH1, GAPDH, HSP90AB1, RPL37A, TPI1, FABP4, S100A6, TOT1, TUBA1B, RPS4X, RPL5, HNRNPK, RPS3A, RPS2, HNRNPA1 | r-µg on the SJ-10 Recoverable Scientific Satellite for 3 and 10 d | [119] |
| Human peripheral blood-derived endothelial progenitor cells | Increase in HIF1A and NOS3 after 12 and 24 h, then decrease after 48 h | s-µg on a 3D-clinostat for 24 h | [120] |
Abbreviations: Days (d); high aspect ratio vessels (HARV); head-down tilt (HDT); hours (h); International Space Station (ISS); random positioning machine (RPM); real microgravity (r-µg); rotating cell culture system (RCCS); simulated microgravity (s-µg); three-dimensional (3D).