Next Article in Journal
Sargassum serratifolium Extract Attenuates Interleukin-1β-Induced Oxidative Stress and Inflammatory Response in Chondrocytes by Suppressing the Activation of NF-κB, p38 MAPK, and PI3K/Akt
Next Article in Special Issue
Retinoid X Receptor Antagonists
Previous Article in Journal
A Short Half-Life αIIbβ3 Antagonist ANTP266 Reduces Thrombus Formation
Previous Article in Special Issue
Liver X Receptors: A Possible Link between Lipid Disorders and Female Infertility
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessReview
Int. J. Mol. Sci. 2018, 19(8), 2307; https://doi.org/10.3390/ijms19082307

Beyond the Foam Cell: The Role of LXRs in Preventing Atherogenesis

1
Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON M5S 3M2, Canada
2
Banting and Best Diabetes Centre, University of Toronto, Toronto, ON M5G 2C4, Canada
3
The Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, University of Toronto, Toronto, ON, M5S 3H2, Canada
*
Author to whom correspondence should be addressed.
Received: 9 July 2018 / Revised: 1 August 2018 / Accepted: 2 August 2018 / Published: 7 August 2018
(This article belongs to the Special Issue Molecular Biology of Nuclear Receptors)
Full-Text   |   PDF [467 KB, uploaded 7 August 2018]   |  

Abstract

Atherosclerosis is a chronic condition associated with cardiovascular disease. While largely identified by the accumulation of lipid-laden foam cells within the aorta later on in life, atherosclerosis develops over several stages and decades. During atherogenesis, various cell types of the aorta acquire a pro-inflammatory phenotype that initiates the cascade of signaling events facilitating the formation of these foam cells. The liver X receptors (LXRs) are nuclear receptors that upon activation induce the expression of transporters responsible for promoting cholesterol efflux. In addition to promoting cholesterol removal from the arterial wall, LXRs have potent anti-inflammatory actions via the transcriptional repression of key pro-inflammatory cytokines. These beneficial functions sparked an interest in the potential to target LXRs and the development of agonists as anti-atherogenic agents. These early studies focused on mediating the contributions of macrophages to the underlying pathogenesis. However, further evidence has since demonstrated that LXRs reduce atherosclerosis through their actions in multiple cell types apart from those monocytes/macrophages that infiltrate the lesion. LXRs and their target genes have profound effects on multiple other cells types of the hematopoietic system. Furthermore, LXRs can also mediate dysfunction within vascular cell types of the aorta including endothelial and smooth muscle cells. Taken together, these studies demonstrate the whole-body benefits of LXR activation with respect to anti-atherogenesis, and that LXRs remain a viable target for the treatment of atherosclerosis, with a reach which extends beyond plaque macrophages. View Full-Text
Keywords: liver X receptors; atherosclerosis; cholesterol efflux; inflammation; macrophage; hematopoiesis; hematopoietic stem cells; neutrophils; endothelial cells; smooth muscle cells liver X receptors; atherosclerosis; cholesterol efflux; inflammation; macrophage; hematopoiesis; hematopoietic stem cells; neutrophils; endothelial cells; smooth muscle cells
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Rasheed, A.; Cummins, C.L. Beyond the Foam Cell: The Role of LXRs in Preventing Atherogenesis. Int. J. Mol. Sci. 2018, 19, 2307.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top