Proteomic Analysis of Aortae from Human Lipoprotein(a) Transgenic Mice Shows an Early Metabolic Response Independent of Atherosclerosis

BackgroundElevated low density lipoprotein (LDL) and lipoprotein(a) are independent risk factors for the development of atherosclerosis. Using a proteomic approach we aimed to determine early changes in arterial protein expression in transgenic mice containing both human LDL and lipoprotein(a) in circulation. Methods and ResultsPlasma lipid analyses showed the lipoprotein(a) transgenic mice had significantly higher lipid levels than wildtype, including a much increased LDL and high density lipoprotein (HDL) cholesterol. Analysis of aortae from lipoprotein(a) mice showed lipoprotein(a) accumulation but no lipid accumulation or foam cells, leaving the arteries essentially atherosclerosis free. Using two-dimensional gel electrophoresis and mass spectrometry, we identified 34 arterial proteins with significantly altered abundance (P ConclusionsOur study shows that human LDL and lipoprotein(a) promote changes in the expression of a unique set of arterial proteins which may be early indicators of the metabolic disturbances preceding atherosclerosis.背景：低密度脂蛋白（low density lipoprotein, LDL）与脂蛋白(a)（lipoprotein(a)）水平升高是动脉粥样硬化发生的独立危险因素。本研究采用蛋白质组学方法，旨在探究循环中携带人类LDL与脂蛋白(a)的转基因小鼠动脉蛋白表达的早期变化。 方法与结果：血浆脂质分析结果显示，脂蛋白(a)转基因小鼠的脂质水平显著高于野生型小鼠，其中低密度脂蛋白胆固醇与高密度脂蛋白（high density lipoprotein, HDL）胆固醇水平均大幅升高。对脂蛋白(a)小鼠主动脉的分析表明，其主动脉内存在脂蛋白(a)沉积，但未出现脂质沉积或泡沫细胞，动脉基本无动脉粥样硬化病变。本研究采用二维凝胶电泳与质谱分析法，共鉴定出34种丰度发生显著变化的动脉蛋白（P < 0.05）。 结论：本研究表明，人类LDL与脂蛋白(a)可诱导动脉蛋白表达谱发生特异性改变，这些改变或可作为动脉粥样硬化发生前代谢紊乱的早期预警指标。