Abstract
Capillary endothelial cells are responsible for homeostatic responses to organismic and environmental stimulations. When malfunctioning, they may cause disease. Exposure to microgravity is known to have negative effects on astronauts’ physiology, the endothelium being a particularly sensitive organ. Microgravity-related dysfunctions are striking similar to the consequences of sedentary life, bed rest, and ageing on Earth. Among different countermeasures implemented to minimize the effects of microgravity, a promising one is artificial gravity. We examined the effects of hypergravity on human microvascular endothelial cells of dermal capillary origin (HMEC-1) treated at 4 g for 15 min, and at 20 g for 15 min, 3 and 6 h. We evaluated cell morphology, gene expression and 2D motility and function. We found a profound rearrangement of the cytoskeleton network, dose-dependent increase of Focal Adhesion kinase (FAK) phosphorylation and Yes-associated protein 1 (YAP1) expression, suggesting cell stiffening and increased proneness to motility. Transcriptome analysis showed expression changes of genes associated with cardiovascular homeostasis, nitric oxide production, angiogenesis, and inflammation. Hypergravity-treated cells also showed significantly improved motility and function (2D migration and tube formation). These results, expanding our knowledge about the homeostatic response of capillary endothelial cells, show that adaptation to hypergravity has opposite effect compared to microgravity on the same cell type.
Highlights
Since the 1960s, after the first orbital flight by Russian Cosmonaut Yuri Gagarin, humans have been spending extended periods of time aboard orbiting spacecrafts where the constant free-fall compensates the attraction of gravity, resulting in microgravity.In space, microgravity induces an adaptive response that leads to a variety of symptoms because virtually all organs and organ systems are affected [1]
HMEC-1 cells were exposed to hypergravity both using the Large Diameter Centrifuge (LDC) (4 g or 20 g for 15 min), within the Spin Your Thesis 2016 campaign at European Space Agency (ESA)-European Space Research and Technology Centre (ESTEC) (Noordwijk, NL), Figure 1, and ordinary centrifuges at the home laboratory (20 g, for 1, 3 and 6 h)
We found that the molecular events registered were associated with a significant increase of 2D migration by HMEC-1 at 3 h, 20 g hypergravity compared to reference cells (Figure 3J–N)
Summary
Microgravity induces an adaptive response that leads to a variety of symptoms because virtually all organs and organ systems are affected [1]. Centrifugation has been tested against simulated and real microgravity in several human studies [6]. In-flight centrifuged crewmembers did not suffer from orthostatic intolerance and spatial disorientation; bed rest-induced cardiovascular deconditioning was reduced [7]. Daily exposure to hypergravity counteracted the muscular atrophy induced by prolonged bed rest [8]. Hypergravity treatment reduced muscle and bone atrophy in rodents exposed to both real and simulated microgravity [9]. Exposure to hypergravity proved to be effective in the treatment of common pathologies and ageing-related problems in different animal models. Hypergravity has been proposed as an intervention to counteract obesity and some of the effects of aging in humans [13]
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