Reactive oxygen species and thiol redox signaling in the macrophage biology of atherosclerosis.

SIGNIFICANCE: Despite the recent decline in the prevalence of cardiovascular diseases, atherosclerosis remains the leading cause of death in industrialized countries. Monocyte recruitment into the vessel wall is a rate-limiting step in atherogenesis. Death of macrophage-derived foam cells promotes lesion progression and the majority of acute complications of atherosclerotic disease (e.g., myocardial infarction) occur in lesions that are intensely infiltrated with monocyte-derived macrophages, underlining the critical roles monocytes and macrophages play in this complex chronic inflammatory disease. RECENT ADVANCES: A rapidly growing body of literature supports a critical role for reactive oxygen species (ROS) in the regulation of monocyte and macrophage (dys)function associated with atherogenesis and macrophage death in atherosclerotic plaque. CRITICAL ISSUES: In this review we highlight the important roles of NADHP oxidase 4 recently identified in monocytes and macrophages and the role of ROS and (thiol) redox signaling in different aspects of monocytes and macrophage biology associated with atherosclerosis. FUTURE DIRECTIONS: Studies aimed at identifying the intracellular targets of ROS involved in redox signaling in macrophages and at elucidating the redox signaling mechanisms that control differentiation, activation, polarization, and death of monocytes and macrophages may ultimately lead to the development of novel preventive and therapeutic strategies for atherosclerosis.