Figure 4.

Major influences of glycation on lipid metabolism and reverse cholesterol transport that favor atherogenesis. Alterations in lipid and lipoprotein metabolism induced by early and advanced glycation favor atherogenesis. In blood circulation, the lipolysis of chylomicrons and VLDLs by the lipoprotein lipase (LPL) is damaged by glycation, inducing plasma triglycerides elevation. The activity of CETP is also stimulated between glycated lipoproteins enabling more cholesterol to be transferred from HDLs to atherogenic lipoproteins and reducing HDL cholesterol. Glycated LDLs are taken up by macrophage scavenger receptors and by the advanced glycosylation end product-specific receptor (AGER). Advanced glycated albumin (AGE-albumin) induces, via AGERs, oxidative stress by enhancing the activity of NADPH oxidase 4 and mitochondrial systems and inflammation. Together, oxidative stress and inflammation lead to ER stress that triggers proteasomal and lysosomal degradation of the ABCA-1 compromising the cholesterol efflux to apo A-I and the generation of HDLs. The activity of (LCAT) is impaired by HDL glycation reducing the lipoprotein maturation. The accumulation of cholesterol and toxic oxysterols in macrophages triggers oxidation, inflammation, and ER stress creating a vicious circle that contributes to atherogenesis, plaque instability, and rupture. Parts of the figure were drawn using Servier Medical Art (https://smart.servier.com/, accessed on 14 December 2021).