Bioactivation of Polycyclic Aromatic Hydrocarbon Carcinogens within the vascular Wall: Implications for Human Atherogenesis

  title={Bioactivation of Polycyclic Aromatic Hydrocarbon Carcinogens within the vascular Wall: Implications for Human Atherogenesis},
  author={Kenneth S. Ramos and Bhagavatula Moorthy},
  journal={Drug Metabolism Reviews},
  pages={595 - 610}
Atherogenesis is a complex pathogenetic process involving a variety of structural and functional deficits within the arterial wall that culminate in the formation of fibrous atherosclerotic plaques. Cigarette smoking is potentially the most remediable contributor to cardiovascular mortality and morbidity. Among the 4000 plus chemicals present in tobacco and tobacco smoke, polycyclic aromatic hydrocarbons (PAHs) have been firmly implicated in the etiology of atherosclerosis in experimental model… 

Genetic and molecular mechanisms of chemical atherogenesis.

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Maternal PAH exposure induced placental toxicity and associated adverse fetal development and hemorrhage in different parts of the fetal body, in particular, marked intradermal and cranial hemorrhage, showing that developing fetal blood vasculature is a target of PAH toxicity.

Activation of Aryl Hydrocarbon Receptor Induces Vascular Inflammation and Promotes Atherosclerosis in Apolipoprotein E−/− Mice

The results suggest that CXCR2 mediates the atherogenic activity of environmental pollutants, such as dioxins, and contributes to the development of atherosclerosis through the induction of a vascular inflammatory response by activating the AhR-signaling pathway.

Polycyclic aromatic hydrocarbons and cytochrome P450 in HIV pathogenesis

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The role of fatty acids and cigarette smoke toxicants in cigarette smoke-induced cardiovascular disease

It is shown that AHR activity and α-linolenic acid (ALA, an n-3 PUFA) are potential biomarkers for CVD risk in young, healthy smokers and it is possible that the biomarkers identified may serve not only as early identification of individuals most at risk of developing CVD, but also as biomarker for future CVDrisk in smokers with early stage CVD.

Role of Polycyclic Aromatic Hydrocarbons as EDCs in Metabolic Disorders

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The goal of this review is to provide a current state-of-the-science of the mechanisms of human lung carcinogenesis mediated by PAHs, the experimental approaches used to study this complex class of compounds, and future directions for research of these compounds.

Studying the effects of polycyclic aromatic hydrocarbons on peripheral arterial disease in the United States.





This review summarizes recent advances in the understanding of biological mechanisms of BaP toxicity at the molecular level, and the role of metabolic intermediates in carcinogenesis, atherogenesis, and teratogenesis.

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    Proceedings of the National Academy of Sciences of the United States of America
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The monooxygenase activity found in the aorta could play a significant role in the etiology and pathogenesis of atherosclerosis in humans by catalyzing the conversion of environmental promutagens to mutagenic initiators and/or cytotoxic factors, thus leading to development of benign, smooth muscle tumors of the inner lining of artery walls.

Modulation of protooncogene expression in rat aortic smooth muscle cells by benzo[a]pyrene.

It is shown that BaP enhances serum-induced protooncogene expression during the early part of the cell cycle in rat aortic SMCs and suggest that binding of BaP to intracellular proteins may play a role in these responses.

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The data suggest that the aortas of induced animals metabolize the BaP in cigarette smoke to carcinogenic and toxic products and that this metabolism may initiate vessel injury and lead to the accelerated atherosclerosis seen in cigarette smokers.

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It is suggested that these pigeon strains might offer a promising system in which to further study the role of target tissue biotransformation in the atherogenic actions of polynuclear aromatic hydrocarbons.

Redox regulation of c-Ha-ras and osteopontin signaling in vascular smooth muscle cells: implications in chemical atherogenesis.

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