Chronic intermittent hypoxia activates nuclear factor-κB in cardiovascular tissues in vivo
Chronic intermittent hypoxia activates nuclear factor-κB in cardiovascular tissues in vivo
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DOI：
10.1016/j.bbrc.2006.03.015
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发表时间：
2006-05-05
影响因子：
3.1
通讯作者：
Liu, SF
中科院分区：
文献类型：
--
作者：
Greenberg, H;Ye, XB;Liu, SF
阻塞性睡眠呼吸暂停（OSA）是心血管疾病发病率和死亡率的重要危险因素。OSA促进心血管疾病发展的机制尚不清楚。在这项研究中，我们测试的假设，慢性暴露于间歇性缺氧和复氧（CIH）是一个主要的病理因素，引起心血管炎症，CIH诱导心血管炎症和病理通过激活NF-κ B B途径。我们证明了小鼠暴露于CIH激活了心血管组织中的NF-κ B，OSA患者的单核细胞NF-κ B活性显著升高，当阻塞性呼吸暂停及其导致的CIH通过夜间CPAP治疗消除时，单核细胞NF-κ B活性显著降低。CIH诱导的NF-κ B B活性升高伴随着NOS蛋白表达的增加，NOS蛋白是一种推定的重要的NF-κ B依赖性基因产物，并且与NOS蛋白表达的增加在时间上相关。因此，CIH介导的NF-κ B活化可能是OSA患者中观察到的连接OSA和心血管病理的分子机制。(c)2006年爱思唯尔公司All rights reserved.
Obstructive sleep apnea (OSA) is an important risk factor for cardiovascular morbidity and mortality. The mechanisms through which OSA promotes the development of cardiovascular disease are poorly understood. In this study, we tested the hypotheses that chronic exposure to intermittent hypoxia and reoxygenation (CIH) is a major pathologic factor causing cardiovascular inflammation, and that CIH-induces cardiovascular inflammation and pathology by activating the NF-kappa B pathway. We demonstrated that exposure of mice to CIH activated NF-kappa B in cardiovascular tissues, and that OSA patients had markedly elevated monocyte NF-kappa B activity, which was significantly decreased when obstructive apneas and their resultant CIH were eliminated by nocturnal CPAP therapy. The elevated NF-kappa B activity induced by CIH is accompanied by and temporally correlated to the increased expression of NOS protein, a putative and important NF-kappa B-dependent gene product. Thus, CIH-mediated NF-kappa B activation may be a molecular mechanism linking OSA and cardiovascular pathologies seen in OSA patients. (c) 2006 Elsevier Inc. All rights reserved.