We have previously shown that MAPK inhibition considerably attenuated pressure induced decreases in expression in vSMC. In these studies, the strain induced decrease in growth was associated with a cyclic strain induced down-regulation of Notch receptors that was Gi protein and ERK1/2 dependent. The significant attenuation of Notch signaling and vSMC development was stopped natural product library subsequent ectopic expression of NICDs. In this context, the current study addressed whether anxiety caused MAPK signaling led to changes in downstream GSK 3b action in these cells. Inhibition of p38 activity and ERK failed to attenuate the strain induced phosphorylation and inactivation of GSK 3b, as the strain induced increase in MAPK activities and inactivation of GSK 3b coincided with a substantial reduction in vSMC proliferation and survival. These data claim that unlike AKT neither ERK nor p38 act upstream of GSK 3b in vSMC to transduce and phospho relay biomechanical stimuli and are therefore unlikely to act because the priming kinases for GSK 3b in a reaction to Messenger RNA (mRNA) cyclic strain. In comparison, inhibition of GSK 3b led to significant increases in both standard quantities of ERK and p38 activity and subsequent attenuation of anxiety caused phospho ERK and p38 activity, respectively. Multiple signaling pathways besides those directed towards GSK 3b are activated by cyclic stress. Nonetheless, our data suggest that the strain induced changes in vSMC hdac3 inhibitor proliferation and apoptosis that arise concomitant with an ERK1/2 dependent attenuation of Notch signaling are clearly due partly to increases in GSK 3b phosphorylation at Ser 9 since inhibition with SB216763 modulates Notch signaling and inhibits the strain induced changes ERK1/2 action and therefore Notch signaling downstream. These data further show that GSK 3b signaling may possibly play a vital role in marketing downstream MAPK signaling in vSMC in response to strain. The practical significance of GSK 3b in modulating vSMC growth in response to changes in cyclic strain was further confirmed in vSMC grown within, and upstream from, a stent in vitro. The stented MVP completely reproduces the technical microenvironment within a stent and mimics the significant decline in arterial wall compliance and distensibility following stent implantation. A reduction in cyclic strain amplitude within the stent triggered a marked increase in vSMC cell development concomitant with an increase in increased Notch1 and GSK 3b service signaling. In related studies, stent implantation in vivo, with the associated lowering of cyclic stress amplitude, activated equally pGSK 3b phosphorylation and AKT while also increasing neointima formation inside the stented rat aorta. Ergo, activation of GSK 3b subsequent stent implantation represents a crucial phospho exchange and transduction mechanism for decreases in cyclic tension within arterial media all through restenosis in vivo.