Table 1: The effects of real or simulated microgravity on different endothelial cell types.

Experimental modelExperimental conditionsEffectsAuthors

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
RWV 72 h or 96 h↑ PGI2 and NOCarlsson et al., 2002
RPM 24–48 h↑ NO
↑ Cav-1 phosphorylation (Tyr 14)
Spisni et al., 2006
RWV 4, 24, 48, 96, 144 h↑↑ hsp70
↓ IL-1α
Remodelling of cytoskeleton
↓ actin
Carlsson et al., 2003
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
Spaceflight 12 dCytoskeletal damage
↑ cell membrane permeability
In readapted cells:
persisting cytoskeletal changes
↓ metabolism and cell growth
Kapitonova et al., 2012
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  
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
RPM 96 hAlteration of proteins regulating cytoskeleton assembly
↓ IL-1α, IL-8, and bFGF
↑ chemokines Rantes and Eotaxin, involved in leukocytes recruitment
Griffoni et al., 2011
RPM 24 h↑ iNOS by a mechanism dependent on suppression of AP-1Wang et al., 2009

Bovine aortic ECs (BAEC)RWV for up to 30 dGrowth 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

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

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

Human EC line EA.hy926RPM 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
RPM 7 daysModulation of genes encoding for signal transduction and angiogenic factors, cell adhesion, membrane transport proteins, or enzymes involved in serine biosynthesisMa et al., 2013
RPM 2 h↑ cellular migration
↑ filopodia and lamellipodia
Actin rearrangements
↑ NO
Shi et al., 2012  
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
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
cytoplasmic rearrangement
↑↑ ABL2 after P1 and P31
Grosse et al., 2012
Parabolic flight (22 s microgravity, 1.8 xg 2 periods of 20 s)Parabolic flight
Actin network rearrangement
↓ FLK1
↑ EZR, MSN, OPN, ANXA2, and BIRC5 after 31P
Wehland et al., 2013
RPM 7, 14, 21, and 28 dDifferent 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
RPM 7 and 28 dDelayed 3D cell growth;
↑ beta(1)-integrin, laminin, fibronectin, α-tubulin in tube-like structures after 4 weeks of culturing
Grimm et al., 2009

Human EC line EA.hy926
Bovine lung microvascular ECS
Bovine pulmonary aortic ECs
Porcine ventricular endocardial ECs
RPM 2 hResults 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

Human dermal microvascular cells (HMEC)RWV, RPM 48 or 96 or 168 h↑ TIMP-2
↑ NO
↓ proteasome activity
Mariotti and Maier, 2008

Murine lung capillary ECs (1G11 cells)RWV 72 h↓ endothelial growth
↑ p21
↓ IL-6
↑ eNOS and NO
Cotrupi et al., 2005

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

Human and bovine microvascular ECsRWV 96 h↑ hsp70 in cells which maintained the capability to proliferate in microgravityCotrupi and Maier 2004

Cocultures of endothelial monolayers, human lymphocytes, immune cells, and myeloleucemic (K-560) cellsSpaceflight (ISS)↑ adhesion of PMA-activated lymphocytes
Retained ability of immune cells to contact, recognize, and destroy oncogenic cells in vitro
Buravkova et al., 2005

Legend: ↑, increased; ↓, decreased.