Department of Biochemistry, University of Otago, Dunedin, New Zealand.
PLoS One. 2012;7(1):e30383. doi: 10.1371/journal.pone.0030383. Epub 2012 Jan 19.
Elevated 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.
Plasma 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<0.05) in lipoprotein(a) transgenic mice compared to wildtype including 17 that showed a ≥2 fold difference. Some proteins of interest showed a similarly altered abundance at the transcript level. These changes collectively indicated an initial metabolic response that included a down regulation in energy, redox and lipid metabolism proteins and changes in structural proteins at a stage when atherosclerosis had not yet developed.
Our 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.
升高的低密度脂蛋白（LDL）和脂蛋白（a）是动脉粥样硬化发展的独立危险因素。本研究采用蛋白质组学方法，旨在确定循环中同时含有人 LDL 和脂蛋白（a）的转基因小鼠动脉蛋白表达的早期变化。
血浆脂质分析显示，脂蛋白（a）转基因小鼠的血脂水平明显高于野生型，包括 LDL 和高密度脂蛋白（HDL）胆固醇显著增加。脂蛋白（a）小鼠的主动脉分析显示脂蛋白（a）的积累，但没有脂质积累或泡沫细胞，使动脉基本上没有动脉粥样硬化。通过二维凝胶电泳和质谱分析，我们在脂蛋白（a）转基因小鼠与野生型相比，鉴定出 34 种动脉蛋白的丰度有明显变化（P<0.05），其中 17 种蛋白的差异≥2 倍。一些感兴趣的蛋白在转录水平也表现出类似的丰度变化。这些变化共同表明存在一种初始的代谢反应，包括能量、氧化还原和脂质代谢蛋白的下调，以及在尚未发生动脉粥样硬化的阶段结构蛋白的变化。
本研究表明，人 LDL 和脂蛋白（a）促进了一组独特的动脉蛋白表达的改变，这些改变可能是动脉粥样硬化发生前代谢紊乱的早期指标。
