Benzo[a]pyrene potentiates the pathogenesis of abdominal aortic aneurysms in apolipoprotein E knockout mice.

Prins PA, Perati PR, Kon V, Guo Z, Ramesh A, Linton MF, Fazio S, Sampson UK
Cell Physiol Biochem. 2012 29 (1-2): 121-30

PMID: 22415081 · PMCID: PMC3711770 · DOI:10.1159/000337593

The objective of this study was to determine the effect of benzo[a]pyrene (BaP), an abundant environmental polycyclic aromatic hydrocarbon compound, on the pathogenesis of abdominal aortic aneurysms (AAA). Earlier studies have shown that BaP promotes vasculopathy, including atherosclerosis, a predisposing factor for AAA development. In two experimental arms, 203 apolipoprotein E knockout (ApoE-/-) mice were evaluated in 4 groups: BaP, angiotensin II (AngII), BaP+AngII and control. Mice in the first arm were exposed to 5mg/kg/week of BaP for 42 days, and in the second arm to 0.71mg/kg daily for 60 days. In arm one, AAA incidence was higher in the BaP+AngII (14/28) versus AngII (8/27) group (p < 0.05), rupture (n=3) was observed only in BaP+AngII treated mice (p < 0.05). In the second arm, AAA incidence did not differ between AngII (17/30) and BaP+AngII (16/29) groups. However, intact AAA diameter was larger in the BaP+AngII (2.3 ± 0.1mm) versus AngII (1.9 ± 0.1mm) group (p < 0.05), but AAA rupture did not differ (p=NS). In both experimental arms, BaP+AngII mice showed increased expression of tumor necrosis factor alpha (TNF-α), cyclophilin A (Cyp A), and matrix metalloproteinase-9 (MMP9) (p < 0.05). No AAA occurred in control or BaP groups. These findings suggest the role of BaP exposure in potentiating AAA pathogenesis, which may have potential public health significance.

Copyright © 2012 S. Karger AG, Basel.

MeSH Terms (15)

Angiotensin II Animals Aorta Aortic Aneurysm, Abdominal Apolipoproteins E Benzo(a)pyrene Cyclophilin A Inflammation Macrophages Male Matrix Metalloproteinase 9 Mice Mice, Inbred C57BL Mice, Knockout Tumor Necrosis Factor-alpha

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