Influence of different forms of fluid shear stress on vascular endothelialTGF-beta 1 mRNA expression

This study investigated the effects of long-term exposure of steady (19 dyn e/cm(2)), 1-Hz non-reversing pulsatile (19+/-6 dyne/cm(2)) and 1-Hz purely oscillatory (0+/-19 dyne/cm(2)) shear stress on endothelial transforming gr owth factor-beta 1 (TGF-beta 1) mRNA expression. Cultured bovine aortic end othelial cells (BAECs) were systematically exposed to the three flow condit ions for periods of 2, 6, 12 and 24 h, and relative differences in TGF-beta 1 mRNA levels were measured by semi-quantitative RT-PCR. In response to st eady shear stress, TGF-beta 1 mRNA levels normalized to no-flow controls we re 1.24, 1.42, 1.30 and 1.47 at the 2-, 6-, 12- and 24-h time points, respe ctively. In response to non-reversing pulsatile flow, these levels were 1.4 9, 1.64, 1.64 and 1.73, while the respective transcript levels for oscillat ory flow were 1.33, 1.12, 1.12 and 1.93. These results indicate that BAEC T GF-beta 1 mRNA was up-regulated with the kinetics of the up-regulation fast er for steady and non-reversing pulsatile flow than for oscillatory flow. G iven the preferential localization of early atherosclerotic lesions in arte rial regions exposed to low and/or oscillatory shear stress and the implica tion of TGF-beta 1 as an athero-protective gene, these results are consiste nt with the notion that regions transiently exposed to oscillatory now may be particularly prone to atherosclerosis.