Figure 1. Inflammation in plaque rupture and thrombosis.

This diagram shows a cross section the intima of part of an artery affected by atherosclerosis. Altered hydrodynamics, illustrated in the upper left, cause loss atheroprotective functions of endothelial cells — including vasodilator, anti-inflammatory, pro-fibrinolytic, and anti-coagulant properties. Antigens presented on antigen-presenting cells such as dendritic cells (DCs) can activate Th1 lymphocytes to produce interferon gamma (IFN-γ), which activates macrophages (MΦ, yellow). Other subtypes of lymphocytes (shown in blue) include Th2 lymphocytes, which can elaborate the anti-inflammatory cytokine interleukin 10 (IL-10) and regulatory T cells that secrete the anti-inflammatory cytokine transforming growth factor beta (TFG-β). On its surface, the macrophage contains Toll-like receptors (TLRs) 2 and 4, which can bind PAMPs and DAMPs (see text). The intracellular TLRs 3, 7, and 9 may also contribute to lipid accumulation and other pro-atherogenic functions of the macrophage. Macrophages can undergo stress of the endoplasmic reticulum (ER) under atherogenic conditions. Cholesterol crystals found in plaques can activate the NLRP3 inflammasome (see text) that can generate mature IL-1β from its inactive precursor. The activated macrophage secretes collagenases that can degrade the triple helical interstitial collagen that lends strength to the plaque's fibrous cap. Activated macrophages also express tissue factor, a potent pro-coagulant, and elaborate pro-inflammatory cytokines that amplify and sustain the inflammatory process in the plaque. When the plaque ruptures due to a collagen-poor, weakened fibrous cap, blood in the lumen can contact tissue factor in the lipid core, triggering thrombus formation (red). When the thrombus forms, polymorphonuclear leukocytes (PMNs) can accumulate and elaborate myeloperoxidase (MPO), which in turn elaborates the potent pro-oxidant hypochlorous acid. Dying PMNs extrude DNA that can form neutrophil extracellular traps (NETs), which can entrap leukocytes and promote thrombosis. Other inflammatory cells modulate atherosclerosis. B2 lymphocytes secrete natural antibody that can inhibit plaque inflammation. On the other hand, B1 lymphocytes, in part via B-cell activating factor (BAFF), can promote inflammation and plaque complication. Mast cells can augment atherogenesis by releasing histamine and the cytokines IFN-γ and IL-6. The consequences of a given plaque rupture depend not only on the solid state of the intimal plaque, but also on the fluid phase of blood, as depicted in the upper right. Systemic inflammation can give rise to cytokines, culminating in the overproduction of IL-6, the trigger of the hepatic acute phase response. The acute phase reactant fibrinogen participates directly in thrombus formation. Another acute phase reactant, plasminogen activator inhibitor-1 (PAI-1), can impair fibrinolysis by inhibiting the endogenous fibrinolytic mediators, urokinase and tissue-type plasminogen activators (uPA and tPA).