Unknown

Dataset Information

0

Activation of aryl hydrocarbon receptor induces vascular inflammation and promotes atherosclerosis in apolipoprotein E-/- mice.


ABSTRACT: Exposure to dioxins has been shown to contribute to the development of inflammatory diseases, such as atherosclerosis. Macrophage-mediated inflammation is a critical event in the initiation of atherosclerosis. Previously, we showed that treatment of macrophages with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to aryl hydrocarbon receptor (AhR)-dependent activation of inflammatory mediators and the formation of cholesterol-laden foam cells. However, the mechanisms responsible for the formation of atherosclerotic lesions mediated through AhR have not been identified.An in vitro macrophage and an apolipoprotein E (ApoE)-/- mouse model were used to determine whether chemokines and their receptors are responsible for the AhR-mediated atherogenesis. Exposure of ApoE-/- mice to TCDD caused a time-dependent progression of atherosclerosis, which was associated with induction of inflammatory genes, including interleukin-8, as well as F4/80 and matrix metalloproteinase-12. A high-fat diet enhanced the TCDD-mediated inflammatory response and aggravated the formation of complex atheromas. Treatment with a CXCR2 inhibitor and an AhR antagonist reduced the TCDD-induced progression of early atherosclerotic lesions in ApoE-/- 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.

SUBMITTER: Wu D 

PROVIDER: S-EPMC3098318 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Activation of aryl hydrocarbon receptor induces vascular inflammation and promotes atherosclerosis in apolipoprotein E-/- mice.

Wu Dalei D   Nishimura Noriko N   Kuo Victoria V   Fiehn Oliver O   Shahbaz Sevini S   Van Winkle Laura L   Matsumura Fumio F   Vogel Christoph Franz Adam CF  

Arteriosclerosis, thrombosis, and vascular biology 20110324 6


<h4>Objective</h4>Exposure to dioxins has been shown to contribute to the development of inflammatory diseases, such as atherosclerosis. Macrophage-mediated inflammation is a critical event in the initiation of atherosclerosis. Previously, we showed that treatment of macrophages with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to aryl hydrocarbon receptor (AhR)-dependent activation of inflammatory mediators and the formation of cholesterol-laden foam cells. However, the mechanisms responsib  ...[more]

Similar Datasets

| S-EPMC4051320 | biostudies-literature
| S-EPMC3117048 | biostudies-literature
| S-EPMC6777860 | biostudies-literature
| S-EPMC4509824 | biostudies-literature
| S-EPMC4890155 | biostudies-other
| S-EPMC5898790 | biostudies-literature
| S-EPMC3865290 | biostudies-literature
| S-EPMC4703891 | biostudies-other
| S-EPMC6358271 | biostudies-literature
| S-EPMC3044199 | biostudies-literature