a Cedars-Sinai Medical Center, The Advanced Clinical Biosystems Research Institute , The Heart Institute , Los Angeles , CA , USA.
b Department of Pathology and Laboratory Medicine , Cedars-Sinai Medical Center , Los Angeles , CA , USA.
Expert Rev Proteomics. 2017 Oct;14(10):869-880. doi: 10.1080/14789450.2017.1374859. Epub 2017 Sep 8.
Apolipoproteins play a key role in pre-, pro-, and anti-atherosclerotic processes and have become important circulating biomarkers for the prediction of cardiovascular disease (CVD) risk. Whereas currently clinical immunoassays are not available for most apolipoproteins and lack the capacity for multiplexing, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) allows simultaneous, highly-specific, and precise quantification of multiple apolipoproteins. Areas covered: We discuss LC-MS/MS methods for quantification of apolipoproteins reported in the literature and highlight key requirements for clinical use. Besides the advances in sample preparation and LC-MS/MS technologies, this overview also discusses advances in proteoform analysis and applications of dried blood/plasma collection. Expert commentary: Standardized quantification using LC-MS/MS technology has been demonstrated for apolipoprotein A-I and B. However, for implementation in clinical CVD risk assessment, LC-MS/MS must bring significant added clinical value in comparison to fast, standardized, and straightforward clinical (immuno)assays. Ongoing advances in accuracy and multiplexing capacity of LC-MS/MS, nonetheless, bear potential to enable standardized and interpretable personalized profiling of a patient's CVD risk by simultaneous quantification of multiple apolipoproteins and -variants. We, moreover, anticipate further personalization of CVD risk assessment by the potential of LC-MS/MS to enable simultaneous genotyping and remote monitoring using dried blood/plasma collection devices.
载脂蛋白在动脉粥样硬化前体、前体和抗动脉粥样硬化过程中发挥着关键作用，已成为预测心血管疾病 (CVD) 风险的重要循环生物标志物。虽然目前大多数载脂蛋白的临床免疫测定法不可用，且缺乏多重检测能力，但液相色谱串联质谱法 (LC-MS/MS) 可同时、高度特异性和精确地定量多种载脂蛋白。涵盖领域：我们讨论了文献中报道的用于定量载脂蛋白的 LC-MS/MS 方法，并强调了其临床应用的关键要求。除了在样品制备和 LC-MS/MS 技术方面的进展外，本综述还讨论了蛋白形式分析和干血/血浆采集应用方面的进展。专家评论：使用 LC-MS/MS 技术进行标准化定量已在载脂蛋白 A-I 和 B 中得到证实。然而，为了在临床 CVD 风险评估中实施，与快速、标准化和直接的临床（免疫）测定相比，LC-MS/MS 必须具有显著的附加临床价值。尽管如此，LC-MS/MS 在准确性和多重检测能力方面的不断进步，有可能通过同时定量多种载脂蛋白和载脂蛋白变体，实现标准化和可解释的患者 CVD 风险个体化分析。此外，我们还预计，LC-MS/MS 能够通过干血/血浆采集设备实现同时基因分型和远程监测，从而进一步实现 CVD 风险评估的个体化。
