TCDD aggravates the formation of the atherosclerotic plaque in ApoE KO mice with a sexual dimorphic pattern.

Aryl hydrocarbon receptor (AhR) ligands are recognized as aggravating factors in cardiovascular diseases but little is known about the role of the AhR in atherosclerosis considering the effects of age and gender. We exposed male and female ApoE knock-out mice, a model to study the pathogenesis of atherosclerosis, to a potent AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by an intraperitoneal injection of 1 μg/kg/week for 8 weeks. Atherosclerotic lesions, histological parameters and critical atherosclerotic markers in aorta were analysed. TCDD increased atherogenic lesions in 35-week old female mice, leading to a switch of vascular smooth muscle cells (VSMCs) from a contractile to a pro-atherogenic phenotype and increased expression for VCAM1. AhR activation accelerates the formation of atherosclerotic plaques with sex and age differences due to the phenotypical switch of VSMCs.