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

Petra A. Prins, Prudhvidhar R. Perati, Valentina Kon, Zhongmao Guo, Aramandla Ramesh, MacRae F. Linton, Sergio Fazio, Uchechukwu K. Sampson

    Research output: Contribution to journalArticle

    8 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)121-130
    Number of pages10
    JournalCellular Physiology and Biochemistry
    Volume29
    Issue number1-2
    DOIs
    StatePublished - 2012

    Keywords

    • Abdominal aortic aneurysm
    • ApoE deficient mice
    • Benzo[a]pyrene
    • Environmental toxicants
    • Inflammation
    • Proteolysis

    ASJC Scopus subject areas

    • Physiology

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