The Notch signalling system is a highly conserved method of cell-to-cell communication involved in cell fate decisions in many cell types. Until recently, the importance of the Notch signalling pathway was recognized in the embryonic but not in the adult vasculature. This project has successfully identified the presence of components of this pathway in adult vascular smooth muscle cells (VSMC). The effect of this pathway on serum deprivation- and cyclic strain-induced VSMC apoptosis has also been determined. This study reports that over-expression of components of the Notch signalling pathway results in a decrease in serum deprivation-induced VSMC apoptosis, whereas endogenous inhibition of the pathway increases apoptosis in these cells. The effect of the Notch signalling pathway on VSMC apoptosis is mediated, at least in part, in a CBF-1-dependent manner. A possible mechanism of the Notch signalling pathway regulation of apoptosis is through interaction with members of the Bcl-2 family of apoptotic proteins. Notch over-expression decreases pro-apoptotic bax, and increases anti-apoptotic bcl-xi expression in VSMC in a CBF-1-dependent manner. In addition, this study has shown previously unreported interaction of the Notch and NFkB signalling pathways in VSMC. Additionally, the effect of cyclic strain, a biomechanical force increased in many vascular disease states, was determined on components of the Notch signalling pathway and also on VSMC apoptosis. Increased cyclic strain results in decreased Notch signalling pathway component expression, and increased apoptosis. Over-expression of the Notch receptor, Notch 3, attenuates the cyclic strain-induced apoptosis in a bcl-xi-caspase 3-dependent manner. In vivo validation of the effects of altered biomechanical forces was performed through analysis of carotid artery, and hepatic portal vein, ligation models. In correlation with the in vitro results obtained, increased alterations in cyclic strain results in an inverse relationship between the Notch signalling pathway and apoptosis in the vessel. These findings may be relevant in the future management of vascular diseases.