Philip Morris International R&D, Quai Jeanrenaud 5, CH-2000 Neuchâtel, Switzerland.
Atherosclerosis. 2012 Dec;225(2):328-34. doi: 10.1016/j.atherosclerosis.2012.09.032. Epub 2012 Oct 10.
Although relationships between smoking and cardiovascular diseases (CVD), and between CVD and lipids are established, the direct impact of smoking on lipidomes is not well understood. We investigated the effect of mainstream cigarette smoke (CS) exposure on plasma, liver, and aorta molecular lipid profiles, and liver transcriptome in the ApoE(-/-) mouse, a well-established mouse model for human atherogenesis.
Plasma, liver, and aorta samples from ApoE(-/-) mice exposed to CS or fresh air (sham) for six months were extracted for lipids using robotic-assisted method and analyzed by mass spectrometry. Gene expression in the liver was obtained on microarrays. Development of atherosclerosis in the aorta was further assessed by plaque size in the aortic arch and lipoprotein concentration in plasma and plaque.
CS increased most lipid classes and molecular lipid species. In plasma, free cholesterol, ceramides, cerebrosides, and most phospholipids were increased in CS-exposed mice. In the liver, several lipid species including free and esterified cholesterol, triacylglycerols, phospholipids, sphingomyelins, and ceramides were elevated. In the aorta, more than 2-fold higher cholesteryl ester (CE), lysophosphatidylcholine, and glucosyl/galactosylceramide levels were seen. Moreover, CS exposure induced a significant decrease in several plasma CE and phosphatidylcholine species that contained polyunsaturated fatty acids. Genes involved in amino acid and lipid metabolism showed perturbed transcription profiles in the liver.
We have quantified some of the molecular changes that accompany the increase of plaque size that is accelerated by CS exposure in the aortae of ApoE(-/-) mice. These results suggest that specific changes in the lipidome and transcriptome, for example in ceramide and polyunsaturated fatty acid species, may be associated with atherosclerosis.
虽然吸烟与心血管疾病（CVD）之间以及 CVD 与脂质之间的关系已得到确立，但吸烟对脂质组的直接影响尚不清楚。我们研究了主流香烟烟雾（CS）暴露对 ApoE（-/-）小鼠血浆、肝脏和主动脉分子脂质谱以及肝脏转录组的影响，ApoE（-/-）小鼠是一种用于人类动脉粥样硬化的成熟小鼠模型。
使用机器人辅助方法提取 CS 或新鲜空气（假）暴露六个月的 ApoE（-/-）小鼠的血浆、肝脏和主动脉样本，并用质谱法分析。使用微阵列获得肝脏中的基因表达。通过主动脉弓中的斑块大小和血浆及斑块中的脂蛋白浓度进一步评估主动脉粥样硬化的发展。
CS 增加了大多数脂质类和分子脂质种类。在血浆中，CS 暴露的小鼠中游离胆固醇、神经酰胺、脑苷脂和大多数磷脂增加。在肝脏中，几种脂质种类，包括游离和酯化胆固醇、三酰基甘油、磷脂、神经鞘磷脂和神经酰胺，都升高了。在主动脉中，胆固醇酯（CE）、溶血磷脂酰胆碱和葡萄糖/半乳糖神经酰胺的水平高出 2 倍以上。此外，CS 暴露导致几种含有多不饱和脂肪酸的血浆 CE 和磷脂种类显著减少。肝脏中参与氨基酸和脂质代谢的基因转录谱发生紊乱。
我们已经定量了一些伴随 CS 暴露加速 ApoE（-/-）小鼠主动脉中斑块大小增加的分子变化。这些结果表明，脂质组和转录组的特定变化，例如神经酰胺和多不饱和脂肪酸种类，可能与动脉粥样硬化有关。
