Signal transduction system in human aortic smooth muscle cell stimulated by pure pressure

Mechanical forces related to pressure and flow are important for cell hypertrophy and proliferation. We hypothesized the presence of mechanosensors that were solely sensitive to pure atmospheric pressure in the absence of shear and tensile stresses. A pressure-loading apparatus was set up to examine the effects of atmospheric pressure on human aortic smooth muscle cells (HASMC). Pressure application of 140 to 180mmHg produced DNA synthesis in a pressure-dependent manner. In contrast, pressure of 120mmHg or less produced no significant change. Pertussis toxin (PTx) completely inhibited the pressure-induced increase of DNA synthesis. Under the high pressure of 200 mmHg. Both extracellular signal-related kinase and c-Jun N-terminal kinase activities, but not p38 activity, were stimulated by pressure of more than 160 mmHg. ACE inhibitor inhibited cell proliferation under the pressure. But the addition of All on ACE inhibitor under the pressure could not recover the cell proliferation. These data suggest that HASMC have a mechanosensing cellular switch for DNA synthesis which is sensitive to pure atmospheric pressure, and that the molecular switch is activated by pressure of more than 140 mmHg. The mechanism of the inhibitory effect of ACE inhibitor on cell proliferation stimulated by pure pressure is under way.