Regulation of pro- and anti-atherogenic cytokines

Despite advances in prevention and treatment, vascular diseases continue to account for significant morbidity and mortality in the developed world. Incidence is expected to worsen as the number of patients with common co-morbidities linked with atherosclerotic vascular disease, such as obesity and diabetes, continues to increase, reaching epidemic proportions. Atherosclerosis is a lipid-driven vascular inflammatory disease involving multiple cell types in various stages of inflammation, activation, apoptosis, and necrosis. One commonality among these cell types is that they are activated and communicate with each other in a paracrine fashion via a complex network of cytokines. Cytokines mediate atherogenesis by stimulating expression of numerous proteins necessary for induction of a host of cellular responses, including inflammation, extravasation, proliferation, apoptosis, and matrix production. Cytokine expression is regulated by a number of transcriptional and post-transcriptional mechanisms. In this context, proteins that control and fine-tune cytokine expression can be considered key players in development of atherosclerosis and also represent targets for rational drug therapy to combat this disease. This review will describe the cellular and molecular mechanisms that drive atherosclerotic plaque progression and present key cytokines that participate in this process. We will also describe RNA binding proteins that mediate cytokine mRNA stability and regulate cytokine abundance. Identification and characterization of the cytokines and proteins that regulate their abundance are essential to our ability to identify therapeutic approaches to ameliorate atherosclerotic vascular disease.