Mass Spectrometric Immunoassay and Multiple Reaction Monitoring as Targeted MS-based Quantitative Approaches in Biomarker Development: Potential Applications to Cardiovascular Disease and Diabetes

摘要

Type 2 diabetes (T2DM) is an important risk factor for cardiovascular disease (CVD)—the leading cause of death in the US. Yet not all subjects with T2DM are at equal risk for CVD complications; the challenge lies in identifying those at greatest risk. Therapies directed towards treating conventional risk factors have failed to significantly reduce this residual risk in T2DM patients. Thus newer targets and markers are needed for the development and testing of novel therapies. Herein we review two complementary mass spectrometry-based approaches—Mass Spectrometric Immunoassay (MSIA) and tandem mass spectrometry as multiple reaction monitoring (MRM)—for the analysis of plasma proteins and post translational modifications (PTMs) of relevance to T2DM and CVD. Together, these complementary approaches allow for high-throughput monitoring of many PTMs and the absolute quantification of proteins near the low picomolar range. In this review article, we discuss the clinical relevance of the HDL proteome and Apolipoprotein A-I PTMs to T2DM and CVD as well as provide illustrative MSIA and MRM data on high density lipoprotein (HDL) proteins from T2DM patients to provide examples of how these mass spectrometry approaches can be applied to gain new insight regarding cardiovascular risk factors. Also discussed are the reproducibility, interpretation and limitations of each technique with an emphasis on their capacities to facilitate the translation of new biomarkers into clinical practice.