Immune mechanisms of atherosclerosis

Atherosclerosis is a chronic inflammatory disease of the arterial wall responsible for most ischemic cardiovascular diseases. Circulating levels of several cytokines are associated with disease burden, and CRP levels predict the risk of future cardiovascular events. Atherosclerosis is initiated in response to various stimuli, mostly modified lipids. Innate immune responses involving both vascular and immune cells, mostly monocytes/macrophages, are rapidly activated in response to vascular injury, play important roles in vascular remodeling, and orchestrate the development of a more specific adaptive immunity. Most lymphocytes of atherosclerotic plaques are CD4+ T cells of the Th1 cell type. They recognize epitopes on native ApoB100 in a MHCII-dependent manner, produce interferon (IFN)-g and promote pro-atherogenic T cell responses. They are counter-regulated by the anti-inflammatory and homeostatic properties of regulatory T cells (Tregs), mainly through IL-10 and TGF-b–dependent pathways. The development of atherosclerosis is also associated with signs of B lymphocyte activation, particularly manifested by enhanced production of natural IgM type and adaptive IgG type antioxidized low-density lipoprotein autoantibodies. Recent studies have redefined the roles of the different B-cell subsets in atherosclerosis. Innate B1-cell subset protects against lesion development in an IgM-dependent manner (Kyaw, 2011 #17924), whereas B2 cells promote atherosclerosis, at least in part through activation of adaptive T-cell responses. I will briefly discuss the most recent advances in our understanding of pro- and antiatherogenic pathways and suggest several new and promising immune-based therapeutic strategies to limit disease progression and severity.