“…In the evening, the increased hydrostatic pressure in the veins of the lower legs, which develops with upright position, is transmitted to the microcirculation. Late at night, hydrostatic pressure is known to play a lesser role and pressures are redistributed 23 ; this has been demonstrated in studies using high-frequency ultrasound 24 and has been reinforced by results of magnetic resonance imaging of the skin. 25 Venous hypertension causes disturbed microcirculation and pathologic changes of the capillaries, with repeated tissue congestion and decongestion, extravasation of red blood cells, and release of proinflammatory cytokines due to activation of monocytes, 26 macrophages, 27 or neutrophils, 28 such as interleukin 1b (IL-1b), IL-6, tumor necrosis factor a, 29 vascular endothelial growth factor, 30 expression of intercellular adhesion molecules, 31 transforming growth factor b1, 32 and mast cell infiltration.…”