Transcriptomic changes in human umbilical cord blood endothelial cells under simulated microgravity.

Microarray analysis of cultured endothelial cells was performed 24 h after simulated microgravity. A significant change in the expression of 177 genes that can be classified into several functional clusters was detected. Among the genes with overexpression, clusters of cell response to external stimuli and regulation of cell motility and proliferation can be reliably distinguished. Among down-regulated genes, clusters of transcription factors with the "zinc fingers" domain and factors involved in the regulation of morphogenesis and angiogenesis were distinguished. The overlapping of signaling pathways involved in mechanotransduction and inflammatory changes is discussed.

[Endothelial Gravisensitivity: the Role of Cytoskeleton and Adhesion Molecules.]

The functions of cardiovascular system are significantly altering in the space flight. The Review discusses the effects of microgravity on endothelial cells, which are important mechanosensitive element of the vascular wall. The challenges of the onboard space experiments are highlighted and current approaches to microgravity simulation in vitro are presented. The role of the cytoskeleton elements as a potential cellular gravisensors are demonstrated. The data on alteration of adhesion molecules expression and its proposed-role in the mechanism of endothelium gravisensitivity regulation is reflected. The possible reasons in the discrepancy of available data are considered in terms of experimental conditions, i.e. cell lines, the duration of exposure, the microgravity model, space flight conditions etc.

Effect of proinflammatory activation on F-actin distribution in cultured human endothelial cells under conditions of experimental microgravity.

We compared the state of actin cytoskeleton, morphology, and expression of VE-cadherin in endothelial cells of human umbilical cord vein under conditions of TNF-α-mediated activation and microgravity modeling and found that 3D-clinorotation for 24 h impaired the integrity of endothelial monolayer, altered cell morphology, induced cytoskeleton reorganization, and reduced the expression of VE-cadherin. The combination of experimental microgravity and proinflammatory activation led to more pronounced clearing of the perinuclear space from microfilaments and accumulation of depolymerized actin, which confirms additive effect of the studied factors on actin cytoskeleton of endothelial cells.

[Effect of modeled microgravity on the secretory activity of cultivated human endothelium cells].

Endothelial cells monolayers are capable to respond to microenvironmental changes immediately by synthesis of vasoactive substances, chemokines, and expression of adhesion molecules. A variety of microgravity models were used to demonstrate the high mechanical and gravity sensitivity of the endothelium. The work was aimed at studying the effects of modeled microgravity on soluble cytokines synthesis by normal and TNF-activated human umbilical vein endotheliocytes. It was found that intact endothelial cells may differ in the ability to secrete IL-6 and IL-8 and that proinflammatory activation increases secretion of these interleukins. Manifestation of this effect is inversely proportional to basal cytokines secretion. Microgravity generated in the Random Positioning Machine does not affect the paracrine effects of proinflammatory induction. This suggests that microgravity is not a proinflammatory stimulant for endothelial cells; at least, it does not increase cytokines secretion or impede the development of inflammatory reaction.

In vitro study of interactions between silicon-containing nanoparticles and human peripheral blood leukocytes.

The effects of silicon dioxide-based nanoparticles on the viability and proliferative activity of human peripheral blood cultured lymphocytes were studied. All nanoparticles in a concentration of 100 µg/ml produced a significant cytotoxic effect, its intensity depending on particles' structure: SiO2 nanoparticles were least toxic, while Ce3(+)-intercaled montmorillonite nanoparticles were most toxic. The cells died mainly by apoptosis and postapoptotic necrosis. Incubation with nanoparticles in a concentration of 100 µg/ml for 72 h caused death of all phytohemagglutinin-activated lymphocytes, while in concentrations of 1 and 10 µg/ml the nanoparticles had no effect of proliferative activity of cells. The results suggest that the effects of nanoparticles on cells are determined by the nanoparticle concentration and size, as well as by their structure.

Effect of sex hormones on levels of mRNAs coding for proteins involved in lipid metabolism in macrophages.

The effects of sex hormones estradiol (E2), testosterone (Te), and 5α-dihydrotestosterone (DT) on cholesterol accumulation induced by modified low density lipoproteins (LDL) in macrophages differentiated from human peripheral blood monocytes and on the levels of mRNAs coding for proteins involved in lipid metabolism have been studied. All three hormones at physiological concentrations (1 nM) are capable of reducing cholesterol accumulation in cells. The treatment of cells with modified and native (not inducing cholesterol accumulation) LDL results in similar alterations in the expression of several mRNAs aimed primarily at homeostatic regulation of lipid metabolism. These alterations depend on the sex of macrophage donors and in some cases are even reversed in cells obtained from male and female donors. The cells not treated with modified LDL have no significant gender differences in the expression of the examined mRNAs. Hormones, either independently or in combination with the modified LDL, influence the levels of some mRNAs, and each hormone shows an individual range of effects. Correlation analysis of changes in mRNA content in the cells showed that the hormones may interfere with coordination of gene expression. Hormone action leads to: (1) reduced coupling of the content of individual mRNAs with their initial levels in the control cells; (2) reduced coupling of different mRNA levels; (3) regrouping of mRNAs between the clusters; and (4) changes in the number of factors that determine the correlation links between mRNAs. The data show that sex hormones may have impact on the level of expression of certain genes and, in particular, on the coordination of gene expression in macrophages.