Emerging roles for cholesterol and lipoproteins in lung disease.
Emerging roles for cholesterol and lipoproteins in lung disease.
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DOI：
10.1016/j.pupt.2012.06.002
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发表时间：
2013-08
影响因子：
3.2
通讯作者：
Fessler MB
中科院分区：
文献类型：
--
作者：
Gowdy KM;Fessler MB
血脂异常，即血清甘油三酯升高、低密度脂蛋白胆固醇升高和/或低密度脂蛋白胆固醇升高，是一个日益受到关注的公共卫生问题。血脂异常与代谢综合征的其他疾病一起影响慢性炎症，并可能源于慢性炎症。脂质失调被认为是动脉粥样硬化性心血管疾病的一个危险因素，但近年来研究表明，脂质失调会影响多个器官系统的多种疾病过程。这篇综述强调了我们目前对胆固醇及其稳态运输在肺生理和病理生理中的作用的理解。基因靶向小鼠缺乏控制逆向胆固醇转运的调节蛋白（例如，ATP结合盒转运蛋白G1，载脂蛋白E），最近被证明具有异常的肺生理，包括对环境的肺先天和适应性免疫反应失调。最近也有研究表明，饮食诱导的血脂异常会改变免疫细胞向肺部的运输，这可能对急性肺损伤、哮喘、肺炎和其他肺部疾病的发病机制具有重要意义。相反，胆固醇靶向药物，如他汀类药物、载脂蛋白模拟肽和肝X受体激动剂，在治疗几种肺部疾病方面已经显示出早期的希望。在充分了解血脂异常作为肺部疾病调节剂的全部含义以及脂质靶向药物作为肺部治疗药物的全部潜力之前，需要更好地了解胆固醇及其转运改变肺部免疫的精确分子机制。
Dyslipidemia, the condition of elevated serum triglycerides, elevated low-density lipoprotein cholesterol, and/or low high-density lipoprotein cholesterol, is a public health problem of growing concern. Dyslipidemia clusters with other disorders of the metabolic syndrome that together influence, and may derive from, chronic inflammation. While best recognized as a risk factor for atherosclerotic cardiovascular disease, lipid dysregulation has recently been shown to influence a variety of disease processes in several organ systems. This review highlights our current understanding of the role of cholesterol and its homeostatic trafficking in pulmonary physiology and pathophysiology. Gene-targeted mice deficient in regulatory proteins that govern reverse cholesterol transport (e.g., ATP Binding Cassette transporter G1, apolipoprotein E) have recently been shown to have abnormal lung physiology, including dysregulated pulmonary innate and adaptive immune responses to the environment. It has also recently been shown that diet-induced dyslipidemia alters trafficking of immune cells to the lung in a manner that may have important implications for the pathogenesis of acute lung injury, asthma, pneumonia, and other lung disorders. Conversely, cholesterol-targeting pharmacologic agents, such as statins, apolipoprotein mimetic peptides, and Liver X Receptor agonists, have shown early promise in the treatment of several lung disorders. An improved understanding of the precise molecular mechanisms by which cholesterol and its trafficking modify pulmonary immunity will be required before the full implications of dyslipidemia as a lung disease modifier, and the full potential of lipid-targeting agents as pulmonary therapeutics, can be realized.
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