Direct physical factors and PGI2 and TXA2 secretions by a human endothelial cell line: in vitro investigation of pressure and shear stress applied independently or in synergy.
The direct effect of two types of mechanical stress was measured through the prostacyclin (PGI2) and thromboxane A2 (TXA2) secretions by a confluent monolayer of cells from the EA.hy926 line. Eight values of constant pressure were applied in the gas phase above the culture medium, around atmospheric pressure taken as a control (0 mm Hg), from -500 to +760 mm Hg. Three amplitudes of sinewave modulated pressure (+/- 40; +/- 80; +/- 160 mm Hg) were explored at a frequency of 1 Hz. Modulated pressure (+/- 40 mm Hg) was also applied synergetically to a shear stress generated under steady state conditions by a rectilinear laminar motion of the medium. The cells remained adherent and exhibited unchanged morphology and viability. Constant pressure or depressure increased both PGI2 and TXA2 release but to an extent depending on the pressure value. Under pressure, the PGI2/TXA2 ratio was unchanged, but was higher under depressure, compared to the control. Pressure modulation strongly stimulated the secretion of PGI2 but had no effect on TXA2. Modulation strongly increased the PGI2/TXA2 ratio to a similar extent for the three amplitudes. Pressure-shear synergy enhanced secretion of PGI2 markedly more than shear stress alone, but the level reached was similar to the one induced by pressure modulation. No cumulative effect on the secretion of PGI2 was observed, whereas TXA2 synthesis undergoes a more than cumulative effect. The PGI2/TXA2 ratio remained unchanged under shear alone or under combined shear-pressure modulation but was higher with the modulated pressure alone. These results demonstrate that pressure has an outstanding effect on secretion that may be origin to local disturbances of the vascular system, thus inducing pathologies such as thrombosis or atherosclerosis.
Laboratoire de Biorhéologie et d'Hydrodynamique Physico-chimique (LBHP), ESA 7057 CNRS, Université Denis-Diderot, Paris, France.
A
A
Bouaziz
M M
MM
de Ficquelmont-Loïzos
A
A
Richert
A
A
Caprani
D000399:Air Pressure; D000704:Analysis of Variance; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D004727:Endothelium / Q000166:cytology / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013314:Stress, Mechanical; D013928:Thromboxane A2 / Q000096:biosynthesis* / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D013928:Thromboxane A2; D011464:Epoprostenol