Advances in quantifying apolipoproteins using LC-MS/MS technology: implications for the clinic

ABSTRACT

Introduction: 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.

KEYWORDS:

• Apolipoproteins
• cardiovascular disease
• mass spectrometry
• laboratory test
• clinical chemistry proteomics
• protein quantification
• trypsin digestion
• peptide selection
• remote monitoring

Acknowledgement

Jennifer Van Eyk receives research support through the Cedars-Sinai Erika J. Glazer endowed chair in Women Heart Health.

Declaration of interest

I. van den Broek received Post-Doctoral Fellowship support from Thermo Fischer Scientific. J. Van Eyk has a sponsored research agreement with Neoteryx, the company that develops the Mitra device for volumetric absorptive microsampling of dried blood samples. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.