A comparison of the mouse and human lipoproteome: suitability of the mouse model for studies of human lipoproteins.
A comparison of the mouse and human lipoproteome: suitability of the mouse model for studies of human lipoproteins.
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DOI：
10.1021/acs.jproteome.5b00213
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发表时间：
2015-06-05
影响因子：
4.4
通讯作者：
Davidson WS
中科院分区：
文献类型：
--
作者：
Gordon SM;Li H;Zhu X;Shah AS;Lu LJ;Davidson WS
低密度脂蛋白（LDL）和高密度脂蛋白（HDL）的血浆水平与人群中的心血管疾病表现出相反的关联，小鼠模型已被大量用于获得对这些关系的机械理解。在人类中，最近的质谱研究表明，血浆脂蛋白质组比原来认识的要复杂得多。这对于HDL尤其如此，HDL包含约90种不同的蛋白质，其中大多数发挥的功能作用超出了简单脂质转运的预期。不幸的是，小鼠的脂蛋白组在很大程度上仍然是未知的，这是一个重大的差距，因为严重依赖于模型。使用凝胶过滤色谱和质谱分析，目标是磷脂结合的血浆蛋白，我们比较了小鼠脂蛋白质组及其大小分布，以前的，相同的人类分析。我们在小鼠中鉴定了113种脂质相关蛋白。一般而言，小鼠和人类的LDL和HDL大小范围的蛋白质多样性相似，但也存在一些明显差异。对于大多数蛋白质，大小分布，即给定蛋白质是否与大或小HDL颗粒相关，例如，在物种之间也相似。然而，少数蛋白质再次表现出明显的差异，这可能反映了物种之间的代谢差异。最后，通过将脂质和蛋白质大小特征相关联，我们确定了五种蛋白质，它们与两个物种中的主要HDL蛋白载脂蛋白A-I密切相关。因此，小鼠具有在人类脂蛋白中鉴定的大多数次要蛋白质，这些蛋白质在炎症、先天免疫、蛋白水解及其抑制和维生素转运中起关键作用。这为继续使用小鼠作为人脂蛋白代谢许多方面的模型提供了支持。
Plasma levels of low density lipoproteins (LDL) and high density lipoproteins (HDL) exhibit opposing associations with cardiovascular disease in human populations and mouse models have been heavily used to derive a mechanistic understanding of these relationships. In humans, recent mass spectrometry studies have revealed that the plasma lipoproteome is significantly more complex than originally appreciated. This is particularly true for HDL which contains some 90 distinct proteins, a majority of which play functional roles that go beyond those expected for simple lipid transport. Unfortunately, the mouse lipoproteome remains largely uncharacterized—a significant gap given the heavy reliance on the model. Using a gel filtration chromatography and mass spectrometry analysis that targets phospholipid-bound plasma proteins, we compared the mouse lipoproteome and its size distribution to a previous, identical human analysis. We identified 113 lipid associated proteins in the mouse. In general, the protein diversity in the LDL and HDL size ranges was similar in mice versus humans, though some distinct differences were noted. For the majority of proteins, the size distributions, that is, whether a given protein was associated with large versus small HDL particles, for example, were also similar between species. Again, however, there were clear differences exhibited by a minority of proteins that may reflect metabolic differences between species. Finally, by correlating the lipid and protein size profiles, we identified five proteins that closely track with the major HDL protein, apolipoprotein A-I across both species. Thus, mice have most of the minor proteins identified in human lipoproteins that play key roles in inflammation, innate immunity, proteolysis and its inhibition, and vitamin transport. This provides support for the continued use of the mouse as a model for many aspects of human lipoprotein metabolism.