Reverse lipid transport is critical to maintain homeostasis. Smoking causes lipid accumulation in macrophages, therefore suggesting suboptimal reverse lipid transport mechanisms. In this study, we investigated the interplay between smoking and reverse lipid transport and the consequences on smoking-induced lung and peripheral alterations. To investigate the relationship between smoking and reverse lipid transport, we used a clinical lung gene expression dataset and a mouse model of cigarette smoke exposure. We also used ApoA-1−/− mice, with reduced reverse lipid transport capacity, and a recombinant ApoA-1 Milano/phospholipid complex (MDCO-216) to boost reverse lipid transport. Cellular and functional analyses were performed on the lungs and impact on body composition was also assessed. Smoking affects pulmonary expression of abca1, abcg1, apoe and scarb1 in both mice and humans, key genes involved in reverse lipid transport. In mice, the capacity of bronchoalveolar lavage fluid and serum to stimulate cholesterol efflux in macrophages was increased after a single exposure to cigarette smoke. ApoA-1−/− mice showed increased lung neutrophilia, larger macrophages and greater loss in lean mass in response to smoking, whereas treatment with MDCO-216 reduced the size of macrophages and increased the lean mass of mice exposed to cigarette smoke. Altogether, this study shows a functional interaction between smoking and reverse lipid transport, and opens new avenues for better understanding the link between metabolic and pulmonary diseases related to smoking. Smoking affects reverse lipid export mechanisms, represent a new pathological mechanism and therapeutic target http://ow.ly/g8pw30dWU8U

中文翻译：

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吸烟与肺逆向脂质转运之间的相互作用

反向脂质转运对于维持体内平衡至关重要。吸烟会导致巨噬细胞中的脂质积累，因此表明逆向脂质转运机制欠佳。在这项研究中，我们调查了吸烟和反向脂质转运之间的相互作用以及对吸烟引起的肺和外周改变的影响。为了研究吸烟与反向脂质转运之间的关系，我们使用了临床肺基因表达数据集和香烟烟雾暴露的小鼠模型。我们还使用了反向脂质转运能力降低的 ApoA-1-/- 小鼠和重组 ApoA-1 Milano/磷脂复合物 (MDCO-216) 来促进反向脂质转运。对肺进行了细胞和功能分析，还评估了对身体成分的影响。吸烟影响 abca1、abcg1、小鼠和人类中的 apoe 和 Scarb1，它们是参与逆向脂质转运的关键基因。在小鼠中，单次接触香烟烟雾后，支气管肺泡灌洗液和血清刺激巨噬细胞胆固醇流出的能力增加。ApoA-1-/- 小鼠表现出肺中性粒细胞增多、巨噬细胞增多和对吸烟的反应更大的瘦体重损失，而用 MDCO-216 治疗减少了巨噬细胞的大小并增加了暴露于香烟烟雾的小鼠的瘦体重。总而言之，这项研究显示了吸烟和反向脂质转运之间的功能相互作用，并为更好地了解与吸烟相关的代谢和肺部疾病之间的联系开辟了新的途径。吸烟影响逆向脂质输出机制，代表一种新的病理机制和治疗靶点 http://ow.