Title: Perspectives on the potential involvement of the AH receptor-dioxin axis in cardiovascular disease.
Authors: Puga, Alvaro
Published In Toxicol Sci, (2011 Apr)
Abstract: The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the induction of the CYP1 family of cytochrome P450s and of several phase II detoxification enzymes. Although induction of these genes is the best characterized AHR function, it does not adequately explain the diversity of AHR-mediated effects. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the prototypical AHR ligand and dioxin congener and a model for many environmentally relevant organochlorinated compounds. Research over the course of the last 30 years has made it evident that AHR activation in response to TCDD and other xenobiotic agonists directly affects multiple metabolic pathways, leading to the identification of many AHR-directed effects of dioxin involved in regulation of growth factor signaling, cell cycle proliferation, differentiation, arrest, and apoptosis. There is ample evidence that TCDD causes persistent cardiac defects in zebrafish, chickens, mice, and likely humans and is associated with human cardiovascular disease. The question that I address here is whether exposure to TCDD during early development perturbs the concerted differentiation patterns of cardiovascular cell lineages and tissues and leads to cardiac malformations and long-term cardiovascular disease. Research to define the mechanisms responsible for the lifelong cardiovascular malformations resulting from TCDD exposure during embryonic development will be highly significant to the prevention of environmental cardiovascular injury.
PubMed ID: 21205634
MeSH Terms: Animals; Cardiovascular Diseases/chemically induced*; Cardiovascular Diseases/metabolism*; Dioxins/toxicity*; Environmental Pollutants/toxicity*; Heart Defects, Congenital/chemically induced; Heart Defects, Congenital/metabolism; Humans; Polychlorinated Dibenzodioxins/toxicity; Receptors, Aryl Hydrocarbon/metabolism*