Figure 1.

Development of the atherosclerotic plaque and effect of LXR activation in the macrophage on the cholesterol homeostasis. (A) When LDL (LDL-C) increases in the blood flow, its concentration is higher in the intima of the arterial walls and its oxidation is favored. This oxidized LDL (oxLDL-C) is absorbed by the macrophages (MΦ), which are transformed into foam cells, full of cholesterol. As these cells are unable to control their cholesterol homeostasis, they enter into apoptosis and secrete inflammatory factors, increasing the recruitment of circulating monocytes in the intima. (B) Activating the nuclear receptors LXRs should promote the efflux of the cholesterol by the ABCs proteins before the macrophages transform into foam cells. Due to, when cholesterol increases, it is transformed into oxysterols. The binding to LXRs with its endogenous ligand or with synthetic LXR agonist complexed with sHDL, such as T0901317 or another selective liver X modulators (SLiMs), will induce two main responses for controlling cholesterol levels: (I) IDOL, a ubiquitin ligase targeting the LDL-receptor (LDLR) is enhanced, which will decrease LDL-cholesterol influx; (II) ABCA1 (as well as ABCG1 non-indicated in this Figure) accumulation is induced as well as cholesterol efflux. Cholesterol will be taken by ApoA1 to form the HDL and in this way favors the reverse cholesterol transport (RCT) to the liver and the atherosclerosis regression. For more details, please refer to the main text.