The proliferation and migration of vascular smooth muscle cells (VSMCs) in the 
intima of an artery, known as intimal hyperplasia, is an important component of 
cardiovascular diseases. This is seen most clearly in the case of in-stent 
restenosis, where drug eluting stents are used to deliver agents that prevent 
VSMC proliferation and migration. One class of agents that are highly effective 
in the prevention of in-stent restenosis is the mammalian Target of Rapamycin 
(mTOR) inhibitors. Inhibition of mTOR blocks protein synthesis, cell cycle 
progression, and cell migration. Key to the effects on cell cycle progression 
and cell migration is the inhibition of mTOR-mediated degradation of p27Kip1 
protein. p27Kip1 is a cyclin dependent kinase inhibitor that is elevated in 
quiescent VSMCs and inhibits the G1 to S phase transition and cell migration. 
Under normal conditions, vascular injury promotes degradation of p27Kip1 protein 
in an mTOR dependent manner. Recent reports from our lab suggest that in the 
presence of diabetes mellitus, elevation of extracellular signal response kinase 
activity may promote decreased p27Kip1 mRNA and produce a relative resistance to 
mTOR inhibition. Here we review these findings and their relevance to designing 
treatments for cardiovascular disease in the presence of diabetes mellitus.