Abstract
Environmental pollutants such as polychlorinated biphenyls (PCBs) may be atherogenic by promoting inflammation and dysfunctional cholesterol metabolism. Previous studies demonstrated that administration of PCB77 to fat‐fed C57BL/6 mice altered liver gene patterns related to cholesterol. This study defined the effects of PCB77 on atherosclerosis in low density lipoprotein receptor (LDLr) deficient mice. Male, LDLr−/− mice were fed a high fat diet (42% kcal as fat) for 3 months, and injected (4 times) with vehicle (0.4 mls safflower oil; n = 8) or PCB77 (49 mg/kg, i.p.; n = 10) every other week during the last 2 months. Body weight and fasting serum glucose concentrations were not different between groups, but liver weight increased in mice administered PCB77 (vehicle: 4.4 ± 0.1; PCB77: 5.5 ± 0.2 gm% body weight; P < 0.05). Total serum cholesterol concentrations were decreased (by 30%) by PCB77 (vehicle: 1250 ± 81; PCB77: 886 ± 48 mg/dL; P < 0.05), and were associated with reduced concentrations of VLDL and LDL. Atherosclerosis (% lesions) in the aortic arch was increased in mice administered PCB77 (vehicle: 9.3 ± 1.3; PCB77: 16.3 ± 2.2 % lesion surface area; P < 0.05). These results demonstrate that despite reductions in pro‐atherogenic lipoproteins, PCB77 augments atherosclerosis in LDLr−/− mice. Further studies are defining mechanisms whereby PCB77 can promote atherosclerosis. (Supported by NIH/NIEHS (P42ES07380).
Published Version
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