Deepening our understanding of HDL proteome

<b>Introduction</b>: High-density lipoprotein (HDL) particles are heterogeneous and their proteome is complex and distinct from HDL cholesterol. However, it is largely unknown whether HDL proteins are associated with cardiovascular protection. <b>Areas covered</b>: HDL isolation techniques and proteomic analyses are reviewed. A list of HDL proteins reported in 37 different studies was compiled and the effects of different isolation techniques on proteins attributed to HDL are discussed. Mass spectrometric techniques used for HDL analysis and the need for precise and robust methods for quantification of HDL proteins are discussed. <b>Expert opinion</b>: Proteins associated with HDL have the potential to be used as biomarkers and/or help to understand HDL functionality. To achieve this, large cohorts must be studied using precise quantification methods. Key factors in HDL proteome quantification are the isolation methodology and the mass spectrometry technique employed. Isolation methodology affects what proteins are identified in HDL and the specificity of association with HDL particles needs to be addressed. Shotgun proteomics yields imprecise quantification, but the majority of HDL studies relied on this approach. Few recent studies used targeted tandem mass spectrometry to quantify HDL proteins, and it is imperative that future studies focus on the application of these precise techniques.

引言：高密度脂蛋白（HDL）颗粒具有异质性，其蛋白质组复杂且有别于高密度脂蛋白胆固醇。然而，目前学界尚不清楚HDL蛋白是否与心血管保护作用相关。
综述范围：本文综述了HDL分离技术与蛋白质组学分析方法。汇编了37项不同研究中报道的HDL蛋白清单，并探讨了不同分离技术对HDL相关蛋白鉴定结果的影响。同时讨论了用于HDL分析的质谱技术，以及精准可靠的HDL蛋白定量方法的必要性。
专家观点：与HDL相关的蛋白有望用作生物标志物，或有助于阐明HDL的功能机制。为实现这一目标，需采用精准定量方法对大型队列开展研究。HDL蛋白质组定量的关键影响因素包括分离方法与所用质谱技术。分离方法会影响HDL中鉴定出的蛋白种类，且需明确其与HDL颗粒结合的特异性。鸟枪法蛋白质组学（shotgun proteomics）的定量结果精度不足，但绝大多数HDL相关研究均采用了该方法。近期仅有少数研究采用靶向串联质谱（tandem mass spectrometry）对HDL蛋白进行定量，因此未来研究亟需聚焦于这类精准技术的应用。