title: Benzo[a]pyrene potentiates the pathogenesis of abdominal aortic aneurysms in apolipoprotein E knockout mice.
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.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-6300, USA.
authors.forename: Petra A
authors.initials: PA
authors.lastname: Prins
authors.forename: Prudhvidhar R
authors.initials: PR
authors.lastname: Perati
authors.forename: Valentina
authors.initials: V
authors.lastname: Kon
authors.forename: Zhongmao
authors.initials: Z
authors.lastname: Guo
authors.forename: Aramandla
authors.initials: A
authors.lastname: Ramesh
authors.forename: MacRae F
authors.initials: MF
authors.lastname: Linton
authors.forename: Sergio
authors.initials: S
authors.lastname: Fazio
authors.forename: Uchechukwu K
authors.initials: UK
authors.lastname: Sampson
mesh_terms: D000804:Angiotensin II / Q000633:toxicity; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000633:toxicity*; D021984:Cyclophilin A / Q000378:metabolism; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D001564:Benzo(a)pyrene; D020780:Matrix Metalloproteinase 9; D021984:Cyclophilin A