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J Vasc Surg. 2014 Feb;59(2):492-9. doi: 10.1016/j.jvs.2013.03.022. Epub 2013 May 12.

Exploration of the mechanisms by which 3,4-benzopyrene promotes angiotensin II-induced abdominal aortic aneurysm formation in mice.

Author information

  • 1Department of Cardiology, The Second Hospital Affiliated to Wenzhou Medical College, Wenzhou, China.
  • 2Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China. Electronic address: llm@fjtcm.edu.cn.
  • 3Department of Cardiology, The Second Hospital Affiliated to Wenzhou Medical College, Wenzhou, China. Electronic address: jefftang@medmail.com.cn.

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.

Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

PMID:
23676189
[PubMed - indexed for MEDLINE]
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