Hypergravity Activates a Pro-Angiogenic Homeostatic Response by Human Capillary Endothelial Cells

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.

Role of Apoptosis in Wound Healing and Apoptosis Alterations in Microgravity

“…The endothelium is probably one of the tissues most affected by gravitational changes regulating basic homeostatic responses such as vascular tone, angiogenesis and inflammation (Davies, 2009;Bryan et al, 2014;De Cesari et al, 2020). Endothelial cells (ECs) are known to react to microgravity by changing their proliferation rate, nitric oxide (NO) production, and cytoskeletal organization (Balsamo et al, 2014;Maier et al, 2015).…”

Gravitational Experimental Platform for Animal Models, a New Platform at ESA’s Terrestrial Facilities to Study the Effects of Micro- and Hypergravity on Aquatic and Rodent Animal Models

“…Artificial gravity has been proposed as a countermeasure to mitigate physiological deconditioning caused by prolonged exposure to weightlessness [ 96 , 97 , 98 ] and therefore to protect human health during long-duration deep space missions. As mentioned in the introduction, immune dysregulation and bone loss are major adverse consequences of spaceflight.…”

Engineered Microsystems for Spheroid and Organoid Studies

“…[204] A more recent paper reports that an increase in length of F-actin and myosin fiber, and hence the improvement in cell motility, is observed in centrifugal conditions (<20 g) in human microvascular endothelial cells (HMEC-1). [205] Moreover, gene analysis showed the upregulations of genes promoting nitric oxide (NO) production, endothelial activation, and angiogenesis, which play key roles in maintaining quiescence in the vascular wall by inhibiting cell proliferation, inflammation, and thrombosis. [206][207][208] Therefore, the centrifugal force environment does not have a fatal effect on cell survival, rather it increases cell proliferation and differentiation rate in some cell types.…”