Emphysema is associated with increased inflammation in lungs of atherosclerosis-prone mice by cigarette smoke: implications in comorbidities of COPD.
Emphysema is associated with increased inflammation in lungs of atherosclerosis-prone mice by cigarette smoke: implications in comorbidities of COPD.
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DOI：
10.1186/1476-9255-7-34
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发表时间：
2010-07-22
期刊：
影响因子：
--
通讯作者：
Rahman I
中科院分区：
文献类型：
--
作者：
Arunachalam G;Sundar IK;Hwang JW;Yao H;Rahman I
慢性阻塞性肺疾病与许多血管影响有关，包括内皮功能障碍、动脉僵硬和动脉粥样硬化。众所周知，吸烟者肺功能的下降与心血管合并症的增加有关。这种由吸烟引起的心肺双重风险的机制尚不清楚。我们研究了易发生动脉粥样硬化的载脂蛋白e缺陷（ApoE-/-）小鼠在CS暴露下发生肺气肿的分子机制。将遗传背景为C57BL/6J的成年雄性和雌性野生型（WT）小鼠和ApoE-/-小鼠暴露于CS，评估肺部炎症反应、氧化应激（脂质过氧化产物）、力学性能和空域扩大。ApoE-/-小鼠肺部炎症反应增强，氧化应激增加，远端空域扩大，肺功能下降。有趣的是，与空气暴露的ApoE-/-小鼠或cs暴露的WT小鼠相比，暴露于cs的ApoE-/-小鼠肺中基质金属蛋白酶（MMP-9和MMP-12）的水平和活性增加，而eNOS水平降低。这些发现表明，CS通过异常的肺部炎症、氧化应激增加以及MMPs和eNOS水平的改变，导致易患心血管异常的小鼠过早肺气肿和肺功能下降。
Chronic obstructive pulmonary disease is associated with numerous vascular effects including endothelial dysfunction, arterial stiffness and atherogenesis. It is also known that a decline in lung function is associated with increased cardiovascular comorbidity in smokers. The mechanism of this cardiopulmonary dual risk by cigarette smoke (CS) is not known. We studied the molecular mechanisms involved in development of emphysema in atherosclerosis-prone apolipoprotein E-deficient (ApoE-/-) mice in response to CS exposure. Adult male and female wild-type (WT) mice of genetic background C57BL/6J and ApoE-/- mice were exposed to CS, and lung inflammatory responses, oxidative stress (lipid peroxidation products), mechanical properties as well as airspace enlargement were assessed. The lungs of ApoE-/- mice showed augmented inflammatory response and increased oxidative stress with development of distal airspace enlargement which was accompanied with decline in lung function. Interestingly, the levels and activities of matrix metalloproteinases (MMP-9 and MMP-12) were increased, whereas the level of eNOS was decreased in lungs of CS-exposed ApoE-/- mice as compared to air-exposed ApoE-/- mice or CS-exposed WT mice. These findings suggest that CS causes premature emphysema and a decline of lung function in mice susceptible to cardiovascular abnormalities via abnormal lung inflammation, increased oxidative stress and alterations in levels of MMPs and eNOS.
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影响因子：
56.9
作者：
MAHLEY, RW
通讯作者：
MAHLEY, RW
DOI：
10.1152/ajplung.00013.2008
发表时间：
2008-05-01
影响因子：
4.9
作者：
Massaro, Donald;Massaro, Gloria DeCarlo
通讯作者：
Massaro, Gloria DeCarlo
影响因子：
37.8
作者：
Knight-Lozano, CA;Young, CG;Ballinger, SW
通讯作者：
Ballinger, SW
影响因子：
6.6
作者：
Edirisinghe, Indika;Arunachalam, Gnanapragasam;Rahman, Irfan
通讯作者：
Rahman, Irfan
影响因子：
5.3
作者：
Ota, Y;Kugiyama, K;Yasue, H
通讯作者：
Yasue, H