The absence of gravity during space flight can alter cardio-vascular functions partially due to reduced physical activity. This affects the overall hemodynamics, and in particular the level of shear stresses to which blood vessels are submitted. Long-term exposure to space environment is thus susceptible to induce vascular remodeling through a mechanotransduction cascade that couples vessel shape and function with the mechanical cues exerted by the circulating cells on the vessel walls. Central to such processes, the glycocalyx – i.e. the micron-thick layer of biomacromolecules that lines the lumen of blood vessels and is directly exposed to blood flow – is a major actor in the regulation of biochemical and mechanical interactions. We discuss in this article several experiments performed under microgravity, such as the determination of lift force and collective motion in blood flow, and some preliminary results obtained in artificial microfluidic circuits functionalized with endothelium that offer interesting perspectives for the study of the interactions between blood and endothelium in healthy condition as well as by mimicking the degradation of glycocalyx caused by long space missions. A direct comparison between experiments and simulations is discussed.