Fig. 4

Proposed model for atherosclerosis development. Reactive oxygen species within arteries causes the oxidation of low-density lipoprotein (LDL). These molecules are bound by neutralizing MDA-OxLDL IgM antibodies, preventing the uptake of these molecules by macrophages. Imbalance between these antibodies and OxLDL results in lipid buildup within macrophages and the conversion to foam cells. These foam cells accumulate inside the intimal wall of the artery where they and cells of the surrounding tissue undergo necroptosis. This results in the release of intercellular antigens which may be modified by the plaque environment. These antigens trigger a polyclonal activation of B cells which form tertiary lymphoid organs and produce autoreactive antibodies. These antibodies then bind Fc receptors on macrophages, smooth muscle cells, and other cells of the innate immune system to produce inflammatory cytokines, propagating inflammation and disease progression