Hypergravity activates a pro-angiogenic homeostatic response by human capillary endothelial cells

Chiara De Cesari, Ivana Barravecchia, Olga V. Pyankova, Matteo Vezza, Marco M. Germani, Francesca Scebba, Jack J.W.A. van Loon, Debora Angeloni*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number2354
JournalInternational Journal of Molecular Sciences
Volume21
Issue number7
DOIs
Publication statusPublished - 1 Apr 2020

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