The effects of mechanical forces on endothelial cell function and behavior are well documented, but have not been fully characterized. Specifically, fluid pressure has been shown to elicit physical and chemical responses known to be involved in the initiation and progression of endothelial cell-mediated vascularization. Central to the process of vascularization is the formation of tube-like structures. This process—tubulogenesis—is essential to both the physiological and pathological growth of tissues. Given the known effects of pressure on endothelial cells and its ubiquitous presence in the vasculature, we investigated pressure as a magnitude-dependent parameter for the regulation of endothelial tubulogenic activity. To accomplish this, we exposed two- and three-dimensional bovine aortic endothelial cell (BAEC) cultures to static pressures of 0, 20, and 40 mmHg for 3 and 4 days. The most significant findings were: (1) cells in two-dimensional culture exposed to 20, but not 40, mmHg exhibited significantly (p \u3c 0.05) increased expression of both VEGF-C and VEGFR-3, and (2) cells in three-dimensional culture exposed to 20, but not 40, mmHg exhibited significant (p \u3e 0.05) increases in endothelial sprouting. These findings evidence the utility of pressure as a selective modulator of tissue microvascularization in vitro and implicates pressure as factor in pathological tubulogenesis in vivo
