Novel Mechanism of Aortic Aneurysm Development in Mice Associated With Smoking and Leukocytes

被引:24
作者
Jin, Jianping [1 ]
Arif, Batool [1 ]
Garcia-Fernandez, Francisca [4 ]
Ennis, Terri L. [1 ]
Davis, Elaine C. [5 ]
Thompson, Robert W. [1 ,2 ,3 ]
Curci, John A. [1 ,6 ]
机构
[1] Washington Univ, Dept Surg, Vasc Surg Sect, Sch Med, St Louis, MO 63110 USA
[2] Washington Univ, Dept Radiol, Sch Med, St Louis, MO 63110 USA
[3] Washington Univ, Dept Cell Biol & Physiol, Sch Med, St Louis, MO 63110 USA
[4] Cardenal Herrera CEU Univ, Dept Physiol Pharmacol & Toxicol, Valencia, Spain
[5] McGill Univ, Dept Anat & Cell Biol, Montreal, PQ, Canada
[6] John Cochran VAMC, Dept Surg, St Louis, MO USA
基金
加拿大健康研究院;
关键词
aneurysms; immunologic techniques; leukocytes; metalloproteinases; smoking; CIGARETTE-SMOKE; NEUTROPHIL RECRUITMENT; MITOCHONDRIAL DAMAGE; EXPOSURE; EXPRESSION; DOXYCYCLINE; ATHEROSCLEROSIS; LOCALIZATION; INHIBITOR; SECRETION;
D O I
10.1161/ATVBAHA.112.300208
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective-The purpose of this study was to evaluate potential mechanisms promoting abdominal aortic aneurysm development with tobacco smoke (TS) exposure. Methods and Results-Experiments used the elastase perfusion model of abdominal aortic aneurysms with smoke-free controls. The effect of TS exposure was evaluated in C57/B16 mice, after broad-spectrum matrix metalloproteinase inhibition with doxycycline and in mice deficient in matrix metalloproteinase-9, matrix metalloproteinase-12, Cathepsin-S, and Neutrophil Elastase. Preparations of washed marrow, spleen, and peripheral blood leukocytes were transferred to smoke-free mice from 6-week TS-exposed mice or smoke-free mice. All mice were euthanized 14 days after elastase perfusion, and the percentage of change in aortic diameter (%Delta aortic diameter) was calculated. Electron microscopy of aortic tissue from animals exposed to TS without elastase exposure did not demonstrate any ultrastructural changes. Neither doxycycline nor any specific elastase deficiency was effective at preventing an increase in %Delta aortic diameter in TS-exposed animals. Smoke exposure for 6 weeks increased the %Delta aortic diameter after a smoke-free interval of up to 6 weeks before elastase perfusion. Leukocyte preparations from TS-exposed mice localized to abdominal aortic aneurysms and increased the %Delta aortic diameter in smoke-free mice. Conclusion-The effect of TS on the development of abdominal aortic aneurysms is not dependent on the activity of elastolytic enzymes and persists for long periods despite cessation of TS. Alterations in leukocyte response to aortic injury appear to mediate this effect. (Arterioscler Thromb Vasc Biol. 2012;32:2901-2909.)
引用
收藏
页码:2901 / +
页数:14
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