The Impact of Microgravity and Hypergravity on Endothelial Cells

Table 1

The effects of real or simulated microgravity on different endothelial cell types.

Experimental model	Experimental conditions	Effects	Authors
Primary human umbilical vein ECs (HUVEC)	Rotating wall vessel (RWV); Random positioning machine (RPM) 48 or 96 h	Growth stimulation; ↑ NO production; Actin remodelling; ↓ Actin	Versari et al., 2007 [12]
	Spaceflight (Progress 40P mission) 10 d	↑ Thioredoxin-interacting protein; ↓ hsp-70 and 90; ↑ secretion of IL-1α and IL-1β; Ion channels (TPCN1, KCNG2, KCNJ14, KCNG1, KCNT1, TRPM1, CLCN4, CLCA2), mitochondrial oxidative phosphorylation, and focal adhesion were widely affected	Versari et al., 2013; [21]
	RWV 72 h or 96 h	↑ PGI2 and NO	Carlsson et al., 2002; [22]
	RPM 24–48 h	↑ NO; ↑ Cav-1 phosphorylation (Tyr 14)	Spisni et al., 2006; [26]
	RWV 4, 24, 48, 96, 144 h	↑↑ hsp70; ↓ IL-1α; Remodelling of cytoskeleton; ↓ actin	Carlsson et al., 2003; [28]
	RPM 24 h	↑ eNOS, Cav-1 and -2; ↓ of the length and width of the cells; ↓ ICAM-1, VCAM-1, E-selectin, and IL-6 and TNF-α	Grenon et al., 2013; [29]
	Spaceflight 12 d	Cytoskeletal damage; ↑ cell membrane permeability; In readapted cells: persisting cytoskeletal changes; ↓ metabolism and cell growth	Kapitonova et al., 2012; [30]
	2D-Clinostat (developed by China Astronaut Research and Training Center) 30 rpm, 24 h	↑ HUVEC tube formation and migration; ↓ number of caveolae in the membrane; ↑ eNOS activity by phosphorylation of Akt and eNOS	Siamwala et al., 2010; [31]
	RWV 5 min, 30 min, 1 h, and 24 h	↑ ICAM-1 expression; Depolymerization of F-actin and clustering of ICAM-1 on cell membrane (short term); Actin fiber rearrangement and stable clustering of ICAM-1 (after 24 h); ↑ ICAM-1 and VCAM-1 RNA after 30 min	Zhang et al., 2010; [32]
	RPM 96 h	Alteration of proteins regulating cytoskeleton assembly; ↓ IL-1α, IL-8, and bFGF; ↑ chemokines Rantes and Eotaxin, involved in leukocytes recruitment	Griffoni et al., 2011; [33]
	RPM 24 h	↑ iNOS by a mechanism dependent on suppression of AP-1	Wang et al., 2009; [34]
Bovine aortic ECs (BAEC)	RWV for up to 30 d	Growth stimulation; ↑ NO; Production of NO dependent on the RWV rotation rate: 73% increase at 8 rpm, 262% increase at 15 rpm, and 500% increase at 20 rpm	Sanford et al., 2002; [35]
Porcine aortic ECs (PAEC)	RPM 72 h	↑ proapoptotic genes (p53, FAS-L, BAX); ↓ antiapoptotic genes (Bcl-2); Dissolution of mitochondrial membrane integrity; Impairment of cell responsiveness to exogenous stimuli	Morbidelli et al., 2005; [11]
Bovine coronary venular ECs (CVEC)	RPM 72 h	↑ Fibronectin (formation of intricate network of FN fibers); ↑ Laminin; ↑ β-Actin (formation of stress fibers); ↑ αβ-Integrin (formation of clusters)	Monici et al., 2011; [36]
Human EC line EA.hy926	RPM 10 days	↑ Caspase-3, Bax, and Bcl-2; ↑ collagen types I and III; Alterations of the cytoskeletal α- and β-tubulins and F-actin; ↓ brain-derived neurotrophic factor, platelet tissue factor, VEGF, and ET-1	Infanger et al., 2007; [37]
	RPM 7 days	Modulation of genes encoding for signal transduction and angiogenic factors, cell adhesion, membrane transport proteins, or enzymes involved in serine biosynthesis	Ma et al., 2013; [38]
	RPM 2 h	↑ cellular migration; ↑ filopodia and lamellipodia; Actin rearrangements; ↑ NO	Shi et al., 2012; [39]
	RPM 4, 12, 24, 48, and 72 h	↑ extracellular matrix (ECM) proteins; Alteration in cytoskeletal components; ↑ expression of ECM proteins (collagen type I, fibronectin, osteopontin, laminin) and flk-1 protein; Morphological and biochemical signs of apoptosis after 4 h, further increasing after 72 h	Infanger et al., 2006; [40]
	Parabolic flight (22 s microgravity, 1.8 xg 2 periods of 20 s)	Parabolic flight; ↓ COL4A5, COL8A1, ITGA6, ITGA10, and ITGB3 mRNAs after P1 (first parabolas); ↑ EDN1 and TNFRSF12A mRNAs after P1; ↓ ADAM19, CARD8, CD40, GSN, PRKCA mRNAs; ↑ PRKAA1 (AMPKα1) mRNAs; cytoplasmic rearrangement; ↑↑ ABL2 after P1 and P31	Grosse et al., 2012; [41]
	Parabolic flight (22 s microgravity, 1.8 xg 2 periods of 20 s)	Parabolic flight; Actin network rearrangement; ↑ CCNA2, CCND1, CDC6, CDKN1A, EZR, MSN, OPN, VEGFA, CASP3, CASP8, ANXA1, ANXA2, and BIRC5; ↓ FLK1; ↑ EZR, MSN, OPN, ANXA2, and BIRC5 after 31P	Wehland et al., 2013; [42]
	RPM 7, 14, 21, and 28 d	Different responsiveness to VEGF and bFGF added exogenously; Altered gene and protein expression of phosphokinase A catalytic subunit, phosphokinase C alpha, and ERK-1 and 2; ↓ VEGF, bFGF, soluble TNFRSF5, TNFSF5, ICAM-1, TNFR 2, IL-18, complement C3, and von Willebrand factor	Grimm et al., 2010; [43]
	RPM 7 and 28 d	Delayed 3D cell growth; ↑ beta(1)-integrin, laminin, fibronectin, α-tubulin in tube-like structures after 4 weeks of culturing	Grimm et al., 2009; [44]
Human EC line EA.hy926; Bovine lung microvascular ECS; Bovine pulmonary aortic ECs; Porcine ventricular endocardial ECs	RPM 2 h	Results indicate that iNOS is a molecular switch for the effects of microgravity on different kinds of endothelial cells; ↑ angiogenesis via the cyclic guanosine monophosphate (cGMP-) PKG dependent pathway	Siamwala et al., 2010; [45]
Human dermal microvascular cells (HMEC)	RWV, RPM 48 or 96 or 168 h	↑ TIMP-2; ↑ NO; ↓ proteasome activity	Mariotti and Maier, 2008; [46]
Murine lung capillary ECs (1G11 cells)	RWV 72 h	↓ endothelial growth; ↑ p21; ↓ IL-6; ↑ eNOS and NO	Cotrupi et al., 2005; [23]
Human pulmonary microvascular ECs (HPMECs)	MG-3 clinostat (developed by the Institute of Biophysics Chinese Academy of Sciences)	↑ apoptosis; ↓ PI3K/Akt pathway; ↑ NF-B and depolymerization of F-actin	Kang et al., 2011; [47]
Human and bovine microvascular ECs	RWV 96 h	↑ hsp70 in cells which maintained the capability to proliferate in microgravity	Cotrupi and Maier 2004; [48]
Cocultures of endothelial monolayers, human lymphocytes, immune cells, and myeloleucemic (K-560) cells	Spaceflight (ISS)	↑ adhesion of PMA-activated lymphocytes; Retained ability of immune cells to contact, recognize, and destroy oncogenic cells in vitro	Buravkova et al., 2005; [49]

Legend: ↑, increased; ↓, decreased.