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

Area of Science:

• Cell Biology
• Space Medicine
• Physiology

Background:

• Capillary endothelial cells maintain homeostasis but are sensitive to environmental changes.
• Microgravity negatively impacts astronaut physiology, mirroring effects of aging and inactivity on Earth.
• Artificial gravity is explored as a countermeasure against microgravity-induced endothelial dysfunction.

Purpose of the Study:

• To investigate the effects of hypergravity on human microvascular endothelial cells (HMEC-1).
• To understand cellular responses to hypergravity, particularly cytoskeleton, focal adhesion kinase (FAK), and Yes-associated protein 1 (YAP1) expression.
• To assess changes in gene expression, motility, and function under hypergravity conditions.

Main Methods:

• HMEC-1 cells were exposed to hypergravity (4g and 20g) for varying durations.
• Evaluated cell morphology, cytoskeleton rearrangement, and FAK/YAP1 phosphorylation.
• Performed transcriptome analysis to identify gene expression changes.
• Assessed cell function through 2D migration and tube formation assays.

Main Results:

• Hypergravity induced significant cytoskeleton rearrangement and increased FAK phosphorylation and YAP1 expression.
• Transcriptome analysis revealed alterations in genes related to cardiovascular homeostasis, nitric oxide production, angiogenesis, and inflammation.
• Cells treated with hypergravity demonstrated enhanced 2D migration and tube formation capabilities.
• Observed opposite effects of hypergravity compared to microgravity on endothelial cells.

Conclusions:

• Hypergravity exposure induces adaptive cellular changes in capillary endothelial cells.
• These adaptations include enhanced cell motility and function, potentially mitigating microgravity-induced damage.
• Findings suggest artificial gravity could be a viable countermeasure for endothelial health in spaceflight and on Earth.