Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

简介：高密度脂蛋白（HDL）颗粒是异质的，其蛋白质组复杂且不同于HDL胆固醇。但是，目前还不清楚HDL蛋白是否与心血管保护有关。

涵盖领域：审查了HDL分离技术和蛋白质组学分析。汇总了37个不同研究中报告的HDL蛋白质列表，并讨论了不同分离技术对归因于HDL的蛋白质的影响。讨论了用于HDL分析的质谱技术以及对定量HDL蛋白的精确鲁棒方法的需求。

专家意见：与HDL相关的蛋白质有潜力用作生物标志物和/或帮助理解HDL功能。为此，必须使用精确的定量方法研究大型队列。HDL蛋白质组定量的关键因素是所采用的分离方法和质谱技术。分离方法学会影响HDL中鉴定出的蛋白质，因此必须解决与HDL颗粒缔合的特异性。gun弹枪蛋白质组学的定量结果不精确，但是大多数HDL研究都依赖于这种方法。很少有最近的研究使用靶向串联质谱法来定量HDL蛋白，因此未来的研究必须专注于这些精确技术的应用。