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Editorial
. 2018 Nov;6(Suppl 1):S28.
doi: 10.21037/atm.2018.09.35.

LXRs are finally being adequately targeted in atherosclerosis

Julio Buñay  1   2 , Silvère Baron  1   2 , Jean-Marc A Lobaccaro  1   2
Affiliations
Editorial

LXRs are finally being adequately targeted in atherosclerosis

Julio Buñay et al. Ann Transl Med. 2018 Nov.
No abstract available

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
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.
See this image and copyright information in PMC

Comment on

References

    1. WHO/2011 Global atlas on cardiovascular disease prevention and control [Internet]. Available online: http://www.who.int/cardiovascular_diseases/publications/atlas_cvd/en/
    1. Shibata N, Glass CK. Macrophages, oxysterols and atherosclerosis. Circ J 2010;74:2045-51. 10.1253/circj.CJ-10-0860 - DOI - PubMed
    1. Maqdasy S, Trousson A, Tauveron I, et al. Once and for all, LXRα and LXRβ are gatekeepers of the endocrine system. Mol Aspects Med. 2016;49:31-46. 10.1016/j.mam.2016.04.001 - DOI - PubMed
    1. Cook IT, Duniec-Dmuchowski Z, Kocarek TA, et al. 24-hydroxycholesterol sulfation by human cytosolic sulfotransferases: formation of monosulfates and disulfates, molecular modeling, sulfatase sensitivity, and inhibition of liver x receptor activation. Drug Metab Dispos Biol Fate Chem 2009;37:2069-37:2 - PMC - PubMed
    1. Lee SD, Tontonoz P. Liver X receptors at the intersection of lipid metabolism and atherogenesis. Atherosclerosis 2015;242:29-36. 10.1016/j.atherosclerosis.2015.06.042 - DOI - PMC - PubMed