Signal transduction in atherosclerosis: second messengers and regulation of cellular cholesterol trafficking

The data summarized in this review demonstrate that the regulation of intracellular cholesterol trafficking is mediated not only by extracellular lipoprotein concentrations and transcriptional responses to alterations in intracellular free cholesterol content. Rather, the modulation of cholesterol trafficking is also regulated by the products synthesized following activation of signal transduction pathways originating at the cell surface. Furthermore, we have identified those cell-derived factors which utilize these signal transduction pathways to elicit alterations in cholesterol trafficking, and demonstrated the importance of the generation of second messengers, most notably eicosanoids, and cyclic AMP in promoting a modulatory influence on specific pro-atherogenic effects of mitogens.