Pro- and Anti-Inflammatory Cytokine Networks in Atherosclerosis

Abstract

Despite advances in prevention and treatment, atherosclerotic vascular disease continues to account for significant morbidity, mortality, and economic burden in the western world. Our current understanding of this disease presents atherosclerosis as a chronic inflammatory process involving multiple cell types in various stages of activation, apoptosis, and necrosis. These cells include monocyte/macrophage, dendritic cells, lymphocytes, endothelial cells, and vascular smooth muscle cells. Activation of these cells and their processes is initiated and sustained by a complex network of soluble factors termed cytokines. Cytokines are produced and recognized by both inflammatory and resident vascular cells, allowing crosstalk between these two systems. Cytokines also regulate the phenotype of many of these cell types. Recognizing functions of these cytokines and their effects on cells which populate atherosclerotic plaque is key to uncovering targets of therapeutic intervention. This paper will present recent studies which describe the cellular protagonists of atherosclerosis and the role they play in formation of atherosclerotic plaque. It will also describe the cytokines which have been identified as produced by and directly affecting dysfunction of these cells. Because atherosclerosis is considered an inflammatory condition, emphasis will be placed on inflammatory cytokines and their effects on atherogenesis. We will conclude with new directions in therapeutic strategies and points of emphasis for future research.