title: Exploration of the mechanisms by which 3,4-benzopyrene promotes angiotensin II-induced abdominal aortic aneurysm formation in mice.
abstract: OBJECTIVE
  This study examined the influence of 3,4-benzopyrene (BaP), a compound found in cigarette smoke, on the formation of angiotensin II (Ang II)-induced abdominal aortic aneurysm (AAA) formation in mice and the underlying mechanisms.
  
  
  METHODS
  C57/B6n mice were divided into four groups. The control group received a weekly intraperitoneal injection of medium-chain triglycerides. The Ang II group received a daily Ang II infusion (0.72 mg/kg) and a weekly intraperitoneal injection of medium-chain triglycerides. The Ang II/BaP group received a daily Ang II infusion (0.72 mg/kg) and a weekly intraperitoneal BaP injection (10 mg/kg, dissolved in medium-chain triglycerides). The BaP group received a weekly intraperitoneal BaP injection (10 mg/kg). After 5 weeks, abdominal aortic diameter was determined. Aortic tissues underwent hematoxylin and eosin, Masson, and immunochemistry staining for evaluation of vascular wall structure, collagen, macrophage infiltration, matrix metalloproteinases (MMPs), and apoptosis.
  
  
  RESULTS
  The Ang II infusion and BaP injection induced AAAs in 41.67% of mice vs 25% in the Ang II group (P < .05). The average aortic diameter increased in the Ang II/BaP group compared with the Ang II group (1.40 ± 0.25 vs 1.2 ± 0.23 mm; P < .05). Average aortic muscular cell apoptosis was higher in the Ang II/BaP group (31% ± 12%) than in the Ang II (19% ± 5%; P < .05) or BaP groups (23% ± 4%; P < .05). Aortic macrophage infiltration and expression of MMP-2, MMP-9, MMP-12, and nuclear factor-κB increased (0.56 ± 0.12, 0.47 ± 0.13, 0.49 ± 0.14, 0.49 ± 0.11, and 0.42 ± 0.12, respectively) in the Ang II/BaP group compared with the Ang II group (0.27 ± 0.08, 0.25 ± 0.06, 0.24 ± 0.09, 0.24 ± 0.09, and 0.23 ± 0.06, respectively; P < .05 for all).
  
  
  CONCLUSIONS
  BaP promotes Ang II-induced AAA formation in mice via elevating infiltration of macrophages, activating nuclear factor-κB, upregulating the expression of MMP-2, MMP-9, and MMP-12, and increasing the apoptosis of vascular muscle cells in its synergistic effect with Ang II in aortic wall.
authors.affiliation: Department of Cardiology, The Second Hospital Affiliated to Wenzhou Medical College, Wenzhou, China.
authors.forename: Kangting
authors.initials: K
authors.lastname: Ji
authors.affiliation: Department of Cardiology, The Second Hospital Affiliated to Wenzhou Medical College, Wenzhou, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Second Hospital Affiliated to Wenzhou Medical College, Wenzhou, China.
authors.forename: Fengchun
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Department of Cardiology, The Second Hospital Affiliated to Wenzhou Medical College, Wenzhou, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Qian
authors.affiliation: Department of Cardiology, The Second Hospital Affiliated to Wenzhou Medical College, Wenzhou, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Cardiology, The Second Hospital Affiliated to Wenzhou Medical College, Wenzhou, China.
authors.forename: Jianjian
authors.initials: J
authors.lastname: Hu
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China. Electronic address: llm@fjtcm.edu.cn.
authors.forename: Lianming
authors.initials: L
authors.lastname: Liao
authors.affiliation: Department of Cardiology, The Second Hospital Affiliated to Wenzhou Medical College, Wenzhou, China. Electronic address: jefftang@medmail.com.cn.
authors.forename: Jifei
authors.initials: J
authors.lastname: Tang
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D007274:Injections, Intraperitoneal; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects; D013997:Time Factors
chemical_list: D016328:NF-kappa B; D000804:Angiotensin II; D001564:Benzo(a)pyrene; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D053508:Matrix Metalloproteinase 12