title: Mass spectrometric immunoassay and MRM as targeted MS-based quantitative approaches in biomarker development: potential applications to cardiovascular disease and diabetes.
abstract: Type 2 diabetes mellitus (T2DM) is an important risk factor for cardiovascular disease (CVD)--the leading cause of death in the United States. Yet not all subjects with T2DM are at equal risk for CVD complications; the challenge lies in identifying those at greatest risk. Therapies directed toward 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 MS-based approaches--mass spectrometric immunoassay (MSIA) and MS/MS as MRM--for the analysis of plasma proteins and 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 high density lipoprotein (HDL) proteome and Apolipoprotein A-I PTMs to T2DM and CVD as well as provide illustrative MSIA and MRM data on HDL proteins from T2DM patients to provide examples of how these MS 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.
authors.affiliation: Department of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Hussein
authors.initials: H
authors.lastname: Yassine
authors.forename: Chad R
authors.initials: CR
authors.lastname: Borges
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Schaab
authors.forename: Dean
authors.initials: D
authors.lastname: Billheimer
authors.forename: Craig
authors.initials: C
authors.lastname: Stump
authors.forename: Peter
authors.initials: P
authors.lastname: Reaven
authors.forename: Serrine S
authors.initials: SS
authors.lastname: Lau
authors.forename: Randall
authors.initials: R
authors.lastname: Nelson
mesh_terms: D000595:Amino Acid Sequence; D015415:Biomarkers / Q000378:metabolism; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D008969:Molecular Sequence Data
chemical_list: D015415:Biomarkers; D001798:Blood Proteins
keywords: Apolipoprotein A-I; Cardiovascular disease (CVD); Diabetes; High density lipoprotein (HDL)