Previously we Benzoylpaeoniflorin reported paradoxical worsening of atherosclerosisat the end of cola beveragesdrinking-treatment. However interpretation of these findings could be questioned considering that determinations had been performed at a single time point immediately after drinking-treatment cessation and the recovery period might have been insufficient to observereversal of damage if any. Present findings confirm that this was not the case indeed. Rate of progression of atherosclerotic lesions increased at different times long after cola drinking-treatment discontinuation. Moreover, the after effects of cola drinking-treatment outweighed those of aging on atherosclerosis time-course. Evodiamine artificially-sweetened cola drinking accelerated progression of atherosclerosis all over the study time and exceeded the effect of aging when age-matched groups were compared. Recently we reported an increase in hepatic transaminases activity, hyperuremia and hypercreatininemia after L drinking in this murine model. Based on these and present findings, we suggest that functional interference at one or more levels and the so derived consequences may be involved in the acceleration of atherosclerosis in ApoE2/2 mice observed long after discontinuation of artificially-sweetened cola drinking. Present findings agree with our recent report and reinforce the idea that ApoE2/2 mice may be idiosyncratically sensitive to the effects of cola beverages drinking on arterial damage. We dare not speculate on possible mechanisms that could at least partially account for the findings in this study, since we have not made determinations thereon. The endothelial dysfunction typically reported in this mouse model might represent a vulnerability trait addressing for cola drinking effects. A deregulation in the complex dialogue between mediators of inflammation, pro-coagulation, peroxidation, to mention a few, and the vascular system might be underlying present findings. Diet habits, aging, gender and lipid profile negatively influence on the endothelial function in ApoE2/2mice through the formation of reactive oxygen species. This scenario favors extensive lipid deposition in the major large arteries and the adhesion and transmigration of circulating monocytes into the aortic intima as well. The activated monocytes in the vascular wall are a source of pro-inflammatory and cytotoxic factors, inducing myofibroblasts�� migration from the media layer and promoting extracellular matrix remodeling. ApoE2/2 mice that did not drink cola beverages showed accelerated changes in atherosclerosis progression which paralleled a rapid increase in liver inflammation around the 20 weeks of age. These results concerning with the natural progression of atherosclerosis lesions in ApoE2/2 mice agree with those reported by Watson et al who found spontaneous acceleration of atherosclerotic lesions around the 20 weeks of life in this murine model as well. The similar time dependence observed for the increase in aortic plaque area and liver inflammation in this study is consistent with a downstream expression of parallel alterations in gene expression in the aorta and liveras reported by other authors. Taken together these findings emphasize the suggested key role for the liver in the process of atherogenesis at least in this murine model.