Shear stress-regulated gene expression in endothelial cells is a central mechanism to mediate endothelial responses to changes in blood flow. This study was done to reveal mechano-sensitive pathways which regulate the expression of METH-1, CD36, TSP-1, Properdin, Tie-2 and angiopoietin-2 in endothelial cells.

HUVEC were exposed to shear stress (6 dyn/cm2, 24 h) while controls were kept under static conditions. The activation of signal transduction pathways was tested with a specific gene array. Three pathways were mainly involved in shear stress transduction: the PLC-pathway, the NFkB- and the p53 system. Expression of flow-regulated genes was analysed by real-time PCR with or without the presence of specific inhibitors of PLC, NO-synthesis, NFkB, and p53.

Shear stress-dependent induction of Tie-2, METH-1, and Properdin was significantly reduced by inhibition of PLC or NO-production. But there was no effect on the suppression of TSP-1, CD36 or angiopoietin-2 by shear stress.

Thus, PLC and NO are both critically involved in shear stress-dependent induction of the genes tested, but so far no pathway has been identified for shear stress-dependent suppression of endothelial genes.