Fig. 3.

Cellular and Molecular Mechanisms of Atherosclerosis and Role of EPA. Mechanisms are depicted in the illustration; effects of EPA are listed to the right indicating increases (↑) or decreases (↓). LDL is subject to oxidative modification, progressing from mm-LDL to ox-LDL. Monocytes attach to endothelial cells, migrate into the subendothelial space, and differentiate into macrophages. Ox-LDL cholesterol uptake leads to foam cell formation. Interactions between macrophage foam cells, Th1 cells, and Th2 cells establish a chronic inflammatory process. Cytokines secreted by lymphocytes and macrophages exert both pro- and anti-atherogenic effects on each of the cellular elements of the vessel wall. SMCs migrate from the medial portion of the arterial wall, proliferate, and secrete extracellular matrix proteins that form a fibrous plaque [75,76]. ACAT, acyl CoA:cholesterol acyltransferase; Apo E, apolipoprotein E; CCR, C–C chemokine receptor; CD, clusters of differentiation; CS, connecting segment; EPA, eicosapentaenoic acid; EPA/AA, eicosapentaenoic acid/arachidonic acid ratio; HDL, high-density lipoprotein; hsCRP, high-sensitivity C-reactive protein; ICAM, intercellular adhesion molecule; IFN, interferon; IL, interleukin; iNOS, inducible nitric oxide synthase; LDL, low-density lipoprotein; LO, lipoxygenase; Lp-PLA₂, lipoprotein-associated phospholipase A₂; MCP, monocyte chemotactic protein; mm-LDL, minimally modified LDL; MMP, matrix metalloproteinase; ox-LDL, oxidized LDL; RLP-C, remnant-like lipoparticle cholesterol; SMC, smooth muscle cell; Th, T helper; VCAM, vascular cell adhesion molecule. Adapted with permission from Atherosclerosis, 242(1), Borow KM, Nelson JR, Mason RP. Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in atherosclerosis, 357–366, copyright 2015, with permission from Elsevier [75].