The development of abdominal aortic aneurysms in mice is enhanced by benzo(a)pyrene.
Cigarette smoking has been strongly associated with abdominal aortic aneurysm (AAA), but the components of tobacco smoke involved in AAA have not been identified. Benzo(a)pyrene (BaP) is an important constituent in cigarette smoke capable of induction of alterations strikingly similar to the pathological changes seen during AAA development. We therefore hypothesized that BaP exposure contributes to the development of AAA. In this study, C57/B6J mice were treated with vehicle, angiotensin II (AngII) (0.72 mg/kg/day), BaP (10 mg/kg/week), or the combination of AngII and BaP, for 5 weeks, and then examined for incidence of AAA and pathological changes of the aortic wall. Results showed that incidence of AAA formation in C57/B6J mice treated with BaP and AngII was significantly higher than that in AngII-treated mice (7 of 12 compared to 2 of 12). Further, five mice in the group treated with AngII/BaP and one in the group treated with AngII exhibited AAA rupture and hematoma. BaP caused macrophage infiltration, disarray of elastic lamella, and loss of vascular smooth muscle cells (VSMCs). We conclude that BaP aggravates AAA formation and rupture in C57/B6J mice by promoting macrophage infiltration, degeneration of elastic lamella, and loss of VSMCs in the aortic wall.
Zhang
Yong
Y
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40202, USA. yong.zhang@louisville.edu
Ramos
Kenneth S
KS
D000804:Angiotensin II; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D001019:Aortic Rupture / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D001564:Benzo(a)pyrene / Q000633:toxicity*; D004195:Disease Models, Animal; D004547:Elastic Tissue / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D012907:Smoking / Q000009:adverse effects*
D000804:Angiotensin II; D001564:Benzo(a)pyrene