Figure 11.

Anthocyanins’ protective effects against atherosclerosis. Anthocyanins’ (ANT) protection occurs in all atherosclerotic stages. ANT decrease plasma low-density lipoprotein (LDL), leading to a reduction in their accumulation in the walls of medium and large arteries. Therefore, ANT indirectly inhibit endothelial cell dysfunction/activation promoted by LDL. Endothelium damage impairs the release of nitric oxide (NO), which together with a local enhanced degradation of NO by increased generation of reactive oxygen species (ROS), decreases NO availability. ANT can increase NO availability by several mechanisms. After activation, endothelia start to express cell adhesion molecules on their surface (ICAM-1, intercellular adhesion molecule-1 and VCAM-1, vascular cell adhesion molecule-1) in order to recruit circulating monocytes to the site of oxidized LDL (oxLDL) accumulation. The expression of these adhesion molecules is downregulated by ANT. In the luminal side, ANT decrease chemokines (CK), which also results in a decline in myeloid cell recruitment. ANT counteract ROS in both the luminal and intimal side, reducing LDL oxidation in vessel wall. During atherogenesis progression, neutrophil-derived granule proteins stimulate macrophage activation to a proinflammatory state which can be inhibited by ANT. Both antioxidant and anti-inflammatory effects of ANT decrease foam cell formation. Moreover, ANT decrease cholesterol by reducing their accumulation in the lipid-rich necrotic core. During the late stages of atherosclerosis, ANT reduce the expression of Toll-like receptor 2 (TLR2) signaling in endothelial cells that regulate neutrophil stimulation of endothelial cell stress and apoptosis. The arrowhead denotes the routes of atherosclerosis progression, whereas the hammerhead represents the effects of ANT.