Journal
PROTEOMICS CLINICAL APPLICATIONS
Volume 7, Issue 7-8, Pages 528-540Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/prca.201200028
Keywords
Apolipoprotein A-I; Cardiovascular disease (CVD); Diabetes; High density lipoprotein (HDL)
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases [R24DK090958]
- American Heart Association [12CRP11750017]
- NIEHS [P30ES06694]
- NIH/NCI [P30CA023074]
- BIO5 Institute of the University of Arizona
- [K23HL107389]
- NATIONAL CANCER INSTITUTE [P30CA023074, R01CA065662] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [K23HL107389] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R24DK090958, R24DK083948] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P30ES006694] Funding Source: NIH RePORTER
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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 approachesmass spectrometric immunoassay (MSIA) and MS/MS as MRMfor 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.
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