Hypergravity affects morphology and function in microvascular endothelial cells

Monici, Monica; Marziliano, Nicola; Basile, Venere; Romano, G.; Conti, Antonio; Pezzatini, Silvia; Morbidelli, Lucia

doi:10.1007/bf02870417

Cited by 18 publications

(30 citation statements)

References 16 publications

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“…Strikingly, at the gene level, a hypergravity-induced reduction of the expression of transcription genes encoding for pro-apoptotic factors (e.g. Fas, FasL and Bcl-XL) and an upregulated expression of the anti-apoptotic factor NFkB was reported for ECs both from micro-and macrovascular origin [11,12]. Although not directly associated with cell viability, these results indicate maintenance of EC survival under hypergravity conditions.…”

Section: Endothelial Cell Morphology and Cytoskeleton Organization Unmentioning

confidence: 81%

“…Overall, loading forces and gravity have essential effects, yet to be fully understood, on the development and homeostasis of several tissues in the human body [9,10]. Concerning angiogenesis, alterations in gravitational force are known to affect EC integrity and behaviour [8,11,12]. In general, previous studies have demonstrated that both phenotype and function of ECs are affected by changes in gravitational force (i.e.…”

Section: Introductionmentioning

confidence: 99%

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Effects of hypergravity on the angiogenic potential of endothelial cells

Costa‐Almeida

Carvalho

Ferreira

et al. 2016

J. R. Soc. Interface.

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Angiogenesis, the formation of blood vessels from pre-existing ones, is a key event in pathology, including cancer progression, but also in homeostasis and regeneration. As the phenotype of endothelial cells (ECs) is continuously regulated by local biomechanical forces, studying endothelial behaviour in altered gravity might contribute to new insights towards angiogenesis modulation. This study aimed at characterizing EC behaviour after hypergravity exposure (more than 1g), with special focus on cytoskeleton architecture and capillary-like structure formation. Herein, human umbilical vein ECs (HUVECs) were cultured under two-dimensional and three-dimensional conditions at 3g and 10g for 4 and 16 h inside the large diameter centrifuge at the European Space Research and Technology Centre (ESTEC) of the European Space Agency. Although no significant tendency regarding cytoskeleton organization was observed for cells exposed to high g's, a slight loss of the perinuclear localization of b-tubulin was observed for cells exposed to 3g with less pronounced peripheral bodies of actin when compared with 1g control cells. Additionally, hypergravity exposure decreased the assembly of HUVECs into capillary-like structures, with a 10g level significantly reducing their organization capacity. In conclusion, short-term hypergravity seems to affect EC phenotype and their angiogenic potential in a time and g-level-dependent manner.

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Section: Endothelial Cell Morphology and Cytoskeleton Organization Unmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Effects of hypergravity on the angiogenic potential of endothelial cells

Costa‐Almeida

Carvalho

Ferreira

et al. 2016

J. R. Soc. Interface.

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“…Because of their location, ECs are continuously exposed to mechanical stress, particularly shear stress, which strongly affects their behaviour (Ali and Schumacker 2002;Spisni et al 2003). Loading alterations are effective too, as widely proved in literature (Carlsson et al 2003;Monici et al 2006). ECs are sensitive both to hyper-and hypogravity conditions, but the mechanisms of mechanotransduction are unknown and different, often contrasting effects have been reported in literature.…”

Section: Introductionmentioning

confidence: 99%

Effect of Hypergravity on Endothelial Cell Function and Gene Expression

Morbidelli

Marziliano

Basile

et al. 2008

Microgravity Sci. Technol

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It is well known that endothelial cells (ECs), which play a major role in cardiovascular system functioning, are very sensitive to mechanical stimuli. It has been demonstrated that changes in inertial conditions (i.e. microgravity and hypergravity) can affect both phenotypic and genotypic expression in ECs. In this report we describe the effects of hypergravity on ECs isolated from bovine aorta (BAECs). ECs were repeatedly exposed to discontinuous hypergravity conditions (5 × 10 min at 10×g with 10 min at 1×g between sets), simulated in a hyperfuge. Then, cell morphology and metabolism were analyzed by autofluorescence techniques. The phenotypic expression of cytoskeleton constituents (β-actin, vimentin, tubulin), adhesion and survival signals (integrins), mediators of inflammation and angiogenesis was evaluated by immunocytofluorescence. Quantitative PCR (Q-PCR) with Low Density Arrays (LDAs) was used to evaluate modifications in gene expression. After hypergravity exposure, no significant changes were observed in cell morphology and energy metabolism. Cells remained adherent to the substratum, but integrin distribution was modified. Accordingly, the cytoskeletal network reorganized, documenting cell activation. There was a reduction in expression of genes controlling vasoconstriction and inflammation. Proapoptotic signals were downregulated. On the whole, the results documented that hypergravity exposure maintained EC survival and function by activation of adaptive mechanisms.

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“…1). Cytoskeleton alterations following the exposure to hypo-and hypergravity have been widely described in many mammalian cell types (Carlsson et al 2003;Uva et al 2002;Monici et al 2006;Searby et al 2005). It is known that cytoskeleton plays an important role in gravisensing (Hughes-Fulford 2003) and cells are able to reorganize the cytoskeletal network in order to adapt their structure to the changed gravitational conditions (Uva et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Hypergravity Effects on Dendritic Cells and Vascular Wall Interactions

Bellik

Parenti

Ledda

et al. 2008

Microgravity Sci. Technol

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Dendritic cells (DCs), the most potent antigen-presenting cells inducing specific immune responses, are involved in the pathogenesis of atherosclerosis. In this inflammatory disease, DCs increase in number, being particularly abundant in the shoulder regions of plaques. Since the exposure to altered gravitational conditions results in a significant impairment of the immune function, the aim of this study was to investigate the effects of hypergravity on both the function of DCs and their interactions with the vascular wall cells. Monocytes from peripheral blood mononuclear cells of healthy volunteers were sorted by CD14+ magnetic beads selection, cultured for 6 days in medium supplemented with GM-CSF and IL-4, followed by a further maturation stimulus. DC phenotype, assessed by flow cytometry, showed a high expression of the specific DC markers CD80, CD86, HLA-DR and CD83. The DCs obtained were then exposed to hypergravitational stimuli and their phenotype, cytoskeleton, ability to activate lymphocytes and interaction with vascular wall cells were investigated. The findings showed that the exposure to hypergravity conditions resulted in a significant impairment of DC cytoskeletal organization, without affecting the expression of DC markers. Moreover, an increase in DC adhesion to human vascular smooth muscle cells and in their ability to activate lymphocytes was observed.

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Hypergravity affects morphology and function in microvascular endothelial cells

Cited by 18 publications

References 16 publications

Effects of hypergravity on the angiogenic potential of endothelial cells

Effects of hypergravity on the angiogenic potential of endothelial cells

Effect of Hypergravity on Endothelial Cell Function and Gene Expression

Hypergravity Effects on Dendritic Cells and Vascular Wall Interactions

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