Novel mechanism of aortic aneurysm development in mice associated with smoking and leukocytes.
Novel mechanism of aortic aneurysm development in mice associated with smoking and leukocytes.
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DOI：
10.1161/atvbaha.112.300208
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发表时间：
2012-12
期刊：
影响因子：
--
通讯作者：
Curci JA
中科院分区：
文献类型：
--
作者：
Jin J;Arif B;Garcia-Fernandez F;Ennis TL;Davis EC;Thompson RW;Curci JA
Evaluate potential mechanisms promoting AAA development with tobacco smoke (TS) exposure. Experiments used the elastase perfusion (EP) model of AAA with smoke-free controls. The effect of TS-exposure was evaluated in C57/Bl6 mice, after broad-spectrum matrix metalloproteinase (MMP)-inhibition with doxycycline and in mice deficient in MMP-9, MMP-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 sacrificed 14 days after EP and the percent change in aortic diameter (%ΔAD) calculated. Before EP, there were no ultrastructural changes, by electron microscopy, in the aorta after TS-exposure. Neither doxycycline nor any specific elastase deficiency was effective at preventing an increased %ΔAD in TS-exposed animals. Smoke-exposure for 6 weeks increased the %ΔAD after a smoke-free interval of up to 6 weeks before EP. Leukocyte preparations from TS-exposed mice localized to AAA and increased the %ΔAD in smoke-free mice. The effect of TS on the development of AAA 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.
