Changes in the physical environment modulate cell responses and may lead to the impairment or even failure of tissue function as a result of mechanotransduction processes. It has been suggested that this situation occurs in some age-related diseases and some pathological conditions observed in space such as cardiovascular deconditioning bone loss muscle atrophy and impaired immune responses. All of these are associated with endothelial dysfunction but the precise mechanism is still unclear. We used the microarray approach to obtain insights into the mechanism responsible for endothelial dysfunction by taking advantage of the challenging environment of gravitational unloading onboard the International Space Station. The effects of gravitational unloading on HUVEC gene expression were investigated by means of cDNA microarray analyses of six randomly chosen samples (three for each of the two conditions of spaceflight and 1g) using Affymetrix Gene Human 1.0 ST Arrays