Study of the effect of gravitational loading variations of human dermal capillary endothelial cells – towards understanding the exploitability of gravity force as a therapeutic treatment

Exposure to microgravity during space flight has negative effects on astronauts’ physiology. Microvascular endothelial cells are among the most sensitive to mechanical stress including gravitational alterations and their dysfunction is mostly responsible for the health problems reported by astronauts and animals returning from space. Although the effects of space flight on astronauts are accelerated and reversible, yet they are striking similar to the consequences of sedentary life, prolong bed rest, senescence and degenerative diseases on Earth. Thus, microgravity might represent a novel model for better understanding common pathologies. A comprehensive cell and molecular biology study is necessary to explain pathophysiological findings after space flight in term of morphological changes and genome variations. In order to better understand the effects of an altered gravitational environment on microvascular endothelial cells (HMEC-1), experiments were performed on board the International Space Station, to study the effects of microgravity, and into Large Diameter Centrifuge, to estimate the effects of hypergravity. The effects of gravitational alterations on HMEC-1 were investigated through the analysis of morphological changes, DNA damage and cell transcriptome. Morphological changes such as reorganisation of cytoskeletal elements and of mitochondria, enlargement of nuclei, signs of DNA damage and repair, and increased apoptotic rate were observed on space flown HMEC-1. Hypergravity also caused modification of cytoskeleton arrangement and gene expression. In some conditions, hypergravity seem to induce an opposite effect to that of microgravity. These findings may provide insights into the origin of the physiological changes occurring in humans and animals during space flight. In the long run, we hope the result of this basic research study will contribute to the creation of preventive and rehabilitative protocols to counteract cardiovascular problems experienced by astronauts, especially of long-term space missions, and more in general by patients affected with cardiovascular pathologies on Earth.