Aryl hydrocarbon receptor pathway: Role, regulation and intervention in atherosclerosis therapy (Review)

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor originally isolated and characterized as the dioxin or xenobiotic receptor. With the discovery of endogenous ligands and studies of AhR knockout mice, AhR has been found to serve an important role in several biological processes, including immune responses and developmental and pathological regulation. In particular, it has been considered as a new major player in cardiovascular diseases. Recent studies have revealed that the development of atherosclerosis is closely associated with AhR function. However, the roles of the AhR in the pathological development of atherosclerosis and atherosclerosis-associated diseases remain unclear. The current review presents the molecular mechanisms involved in the regulation of AhR expression during inflammation, oxidative stress and lipid deposition. Additionally, the role of the AhR in atherosclerosis and atherosclerosis-associated diseases is reviewed.

Evidence that a deviation in the kynurenine pathway aggravates atherosclerotic disease in humans

“…The proposed mechanism for this increase was that transcription factor 21 (TCF21) could cooperate with AhR to activate inflammatory genes in SMCs that could contribute to coronary artery disease (CAD) [76]. Whilst this study suggests a deleterious role for AhR in the process of atherosclerosis, association studies investigating the relationships of AhR signalling with the risk and complications of atherosclerosis‐associated diseases are not conclusive [77]. Excitingly, recent evidence suggests that AhR can exert bidirectional effects on the regulation of inflammation, depending on the availability of external AhR ligands; in the absence of external ligands, AhR can mediate pro‐inflammatory effects [78].…”

A systematic review and meta-analysis on the efficacy of statins in the treatment of atherosclerosis

“…Research in the field of biomedicine has found that statins demonstrate good effects on lowering blood lipids and improving vascular endothelium. Lowering blood lipids mainly involves reducing cholesterol in serum, liver, and aorta, and lowering very low-density lipoprotein cholesterol (VLDL-C) and LDL-C, which can effectively prevent coronary heart disease and delay atherosclerosis (7)(8)(9). However, as few meta-analyses have been conducted on the effects of statins in the treatment of atherosclerosis, and there have been limitations in the existing studies such as small sample size and different research focuses, it is impossible to effectively judge the actual treatment effects of statins on atherosclerosis (10).…”

Progress in research on effect of PM2.5 on occurrence and development of atherosclerosis

“…Activation of AhR may promote the development of AS through a series of inflammatory responses (Fardel, 2013; Lawal, 2017; Wu et al, 2011). A recent review presented the expression and regulatory roles of AhR in the development of AS, including inflammation, oxidative stress, and lipid infiltration (Zhu et al, 2019). However, the mechanism of AhR‐mediated atherogenesis is still unclear, and further exploration of downstream signaling pathways is needed.…”