Current basis for discovery and development of aryl hydrocarbon receptor antagonists for experimental and therapeutic use in atherosclerosis

Pernomian, Laena; Silva, Carlos Henrique Tomich de Paula da

doi:10.1016/j.ejphar.2015.06.058

Cited by 21 publications

(18 citation statements)

References 48 publications

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“…43 Our demonstration of AHR activation during CKD provides a rationale to target it and try to limit the harmful effects of uremic toxins on vascular outcome. 44 Few therapies are available to reduce the effects of uremic toxins that are poorly dialyzable as indolic toxins. Here, we showed that the AHR-AP of serum could be decreased by an AHR antagonist.…”

Section: Discussionmentioning

confidence: 99%

Aryl hydrocarbon receptor is activated in patients and mice with chronic kidney disease

Dou

Poitevin

Sallée

et al. 2018

Kidney International

100

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Section: Discussionmentioning

confidence: 99%

Aryl hydrocarbon receptor is activated in patients and mice with chronic kidney disease

Dou

Poitevin

Sallée

et al. 2018

Kidney International

100

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“…both up- and down-regulation of ROS formation. This delicate balance occurs in such seemingly unrelated signaling pathways as: circadian rhythmicity (Patel et al , 2014); enhanced immune response exhibiting increased levels of inflammatory cytokines and decreased Socs2 (suppression of cytokine signaling-2) expression — that had been observed in zymosan-caused peritonitis in liver of Cyp1a1 / 1a2 / 1b1(−/−) triple-knockout mice (Nebert and Karp, 2008) — and infectious myocarditis (Barroso et al , 2016); inflammatory plaque formation during atherosclerosis (Marinkovic et al , 2013; Uno et al , 2014; Pernomian and da Silva, 2015); hepatic steatosis (Gooley, 2016; Mellor et al , 2016; Nault et al , 2017); atopic dermatitis associated with a dysfunctional skin barrier (Nomura and Kabashima, 2016); and aging and age-associated diseases (Gasiewicz et al , 2014; Patel et al , 2014). …”

Section: Ahr and Cell-signaling Pathwaysmentioning

confidence: 99%

Aryl hydrocarbon receptor (AHR): “pioneer member” of the basic-helix/loop/helix per - Arnt - sim (bHLH/PAS) family of “sensors” of foreign and endogenous signals

Nebert

2017

Progress in Lipid Research

220

191

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The basic-helix-loop-helix Per-Arnt-Sim (bHLH/PAS) family comprises many transcription factors, found throughout all three kingdoms of life; bHLH/PAS members “sense” innumerable intracellular and extracellular “signals” — including endogenous compounds, foreign chemicals, gas molecules, redox potential, photons (light), gravity, heat, and osmotic pressure. These signals then initiate downstream signaling pathways involved in responding to that signal. The term “PAS”, abbreviation for “Per-Arnt-Sim” was first coined in 1991. Although the mouse Arnt gene was not identified until 1991, evidence of its co-transcriptional binding partner, aryl hydrocarbon receptor (AHR), was first reported in 1974 as a “sensor” of foreign chemicals, up-regulating cytochrome P450 family 1 (CYP1) and other enzyme activities that usually metabolize the signaling chemical. Within a few years, AHR was proposed also to participate in inflammation. The mouse [Ah] locus was shown (1973–1989) to be relevant to chemical carcinogenesis, mutagenesis, toxicity and teratogenesis, the mouse Ahr gene was cloned in 1992, and the first Ahr(−/−) knockout mouse line was reported in 1995. After thousands of studies from the early 1970s to present day, we now realize that AHR participates in dozens of signaling pathways involved in critical-life processes, affecting virtually every organ and cell-type in the animal, including many invertebrates.

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“…Risk factors for cardiovascular diseases include vascular senescence and obesity. Chronic vascular inflammation and oxidative stress contribute to atherosclerosis [ 84 , 85 ], but the molecular mechanisms are not well understood. Exposure to contaminants containing ligands of AhR (dioxins, TCDD, PAH, benzo( α )pyrene) are thought to promote the development and progression of atherosclerosis, indicating that AhR may play a role in the regulation of atherosclerosis [ 9 , 86 – 88 ].…”

Section: Ahr As a Therapeutic Target In Cardiovascular Diseasesmentioning

confidence: 99%

Aryl Hydrocarbon Receptor: A New Player of Pathogenesis and Therapy in Cardiovascular Diseases

Tao

Wang

Zhu

et al. 2018

BioMed Research International

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The aryl hydrocarbon receptor (AhR) is a DNA binding protein that acts as a nuclear receptor mediating xenobiotic metabolism and environmental responses. Owing to the evolutionary conservation of this gene and its widespread expression in the immune and circulatory systems, AhR has for many years been almost exclusively studied by the pharmacological/toxicological field for its role in contaminant toxicity. More recently, the functions of AhR in environmental adaption have been examined in the context of the occurrence, development, and therapy of cardiovascular diseases. Increasing evidence suggests that AhR is involved in maintaining homeostasis or in triggering pathogenesis by modulating the biological responses of critical cell types in the cardiovascular system. Here, we describe the structure, distribution, and ligands of AhR and the AhR signaling pathway and review the impact of AhR on cardiovascular physiology. We also discuss the potential contribution of AhR as a new potential factor in the targeted treatment of cardiovascular diseases.

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Current basis for discovery and development of aryl hydrocarbon receptor antagonists for experimental and therapeutic use in atherosclerosis

Cited by 21 publications

References 48 publications

Aryl hydrocarbon receptor is activated in patients and mice with chronic kidney disease

Aryl hydrocarbon receptor is activated in patients and mice with chronic kidney disease

Aryl hydrocarbon receptor (AHR): “pioneer member” of the basic-helix/loop/helix per - Arnt - sim (bHLH/PAS) family of “sensors” of foreign and endogenous signals

Aryl Hydrocarbon Receptor: A New Player of Pathogenesis and Therapy in Cardiovascular Diseases

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