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Received Nov 25, 2017; Revised Mar 14, 2018; Accepted Apr 5, 2018
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1. Introduction
Aryl hydrocarbon receptor (AhR) is a ligand-activated transcriptional factor belonging to the superfamily of basic helix-loop-helix/Per-ARNT-Sim (bHLH/PAS) [1], and is the only member of this family known to bind naturally occurring xenobiotics [2]. Traditionally AhR acts as a crucial regulator mediating xenobiotic metabolism and environmental responses, and it was discovered to bind closely with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and then was hyperactivated to release a myriad of toxicologic outcomes, which contribute to the potency of TCDD as an inducer or promoter of some carcinogenesis in 1982 [3, 4]. Thus, for many years, AhR has been almost exclusively studied by the toxicological field for its role in various environmental and food contaminants such as polycyclic aromatic hydrocarbons, polychlorinated biphenyls and dioxins. Numerous studies have found that cytosolic AhR can be activated by many natural and synthetic ligands, and translocated into the nucleus where it complexes with the AhR nuclear translocator (ARNT) [5]. The complex recognizes the specific dioxin-responsive elements (DREs) and modulates subsequent transcription of its downstream target genes including phase I and phase II metabolic enzymes, which can affect the metabolism of environmental toxicants and chemical substances [6].
The increasing deterioration of the natural environment is having serious consequences on human health. The circulation system is the major organ exposed xenobiotics and endobiotics during metabolic homeostasis [7], and long-term exposure to environmental pollutants can drastically alter this system, resulting in cardiovascular diseases such as hypertension, atherosclerosis, and ischemic heart disease [8–12]. Because many environmental pollutants contain exogenous aryl hydrocarbon receptor (AhR) ligands, increasing attention is being given to the relationship between AhR and cardiovascular diseases. Recent evidence from gene knock-out studies and clinical trials suggests that not only does AhR have a major impact on general physiological functions, including immune responses, reproduction, oxidative stress, tumor promotion, the cell cycle, and proliferation [13, 14], but also influences cardiovascular physiological functions [15–18].
In this review, we discuss the progress of AhR biology and toxicology, its pathophysiology roles in the heart and vascular systems, and...