PMID- 23696124 OWN - NLM STAT- MEDLINE DCOM- 20140611 LR - 20220321 IS - 1862-8354 (Electronic) IS - 1862-8346 (Print) IS - 1862-8346 (Linking) VI - 7 IP - 7-8 DP - 2013 Aug TI - Mass spectrometric immunoassay and MRM as targeted MS-based quantitative approaches in biomarker development: potential applications to cardiovascular disease and diabetes. PG - 528-40 LID - 10.1002/prca.201200028 [doi] AB - 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. CI - (c) 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Yassine, Hussein AU - Yassine H AD - Department of Medicine, University of Southern California, Los Angeles, CA, USA. FAU - Borges, Chad R AU - Borges CR FAU - Schaab, Matthew R AU - Schaab MR FAU - Billheimer, Dean AU - Billheimer D FAU - Stump, Craig AU - Stump C FAU - Reaven, Peter AU - Reaven P FAU - Lau, Serrine S AU - Lau SS FAU - Nelson, Randall AU - Nelson R LA - eng GR - R24 DK083948/DK/NIDDK NIH HHS/United States GR - P30 CA023074/CA/NCI NIH HHS/United States GR - P30CA023074/CA/NCI NIH HHS/United States GR - P30ES06694/ES/NIEHS NIH HHS/United States GR - K23 HL107389/HL/NHLBI NIH HHS/United States GR - K23HL107389/HL/NHLBI NIH HHS/United States GR - P30 ES006694/ES/NIEHS NIH HHS/United States GR - R01 CA065662/CA/NCI NIH HHS/United States GR - R24DK090958/DK/NIDDK NIH HHS/United States GR - R24 DK090958/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20130709 PL - Germany TA - Proteomics Clin Appl JT - Proteomics. Clinical applications JID - 101298608 RN - 0 (Biomarkers) RN - 0 (Blood Proteins) SB - IM MH - Amino Acid Sequence MH - Biomarkers/metabolism MH - Blood Proteins/chemistry/metabolism MH - Cardiovascular Diseases/blood/*metabolism MH - Diabetes Mellitus/blood/*metabolism MH - Humans MH - Immunoassay/*methods MH - Mass Spectrometry/*methods MH - Molecular Sequence Data PMC - PMC4029342 MID - NIHMS576417 OTO - NOTNLM OT - Apolipoprotein A-I OT - Cardiovascular disease (CVD) OT - Diabetes OT - High density lipoprotein (HDL) COIS- The authors have no conflicts of interest to disclose. EDAT- 2013/05/23 06:00 MHDA- 2014/06/12 06:00 PMCR- 2014/08/01 CRDT- 2013/05/23 06:00 PHST- 2012/04/25 00:00 [received] PHST- 2013/02/04 00:00 [revised] PHST- 2013/03/30 00:00 [accepted] PHST- 2013/05/23 06:00 [entrez] PHST- 2013/05/23 06:00 [pubmed] PHST- 2014/06/12 06:00 [medline] PHST- 2014/08/01 00:00 [pmc-release] AID - 10.1002/prca.201200028 [doi] PST - ppublish SO - Proteomics Clin Appl. 2013 Aug;7(7-8):528-40. doi: 10.1002/prca.201200028. Epub 2013 Jul 9.