Mass spectrometric immunoassay and MRM as targeted MS-based quantitative approaches in biomarker development: Potential applications to cardiovascular disease and diabetes
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 tr...
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| Published in | Proteomics. Clinical applications Vol. 7; no. 7-8; pp. 528 - 540 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Germany
Blackwell Publishing Ltd
01.08.2013
Wiley Subscription Services, Inc |
| Subjects | |
| Online Access | Get full text |
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| 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. |
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| AbstractList | 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. 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. [PUBLICATION 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.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. |
| Author | Reaven, Peter Lau, Serrine S. Schaab, Matthew R. Stump, Craig Billheimer, Dean Nelson, Randall Yassine, Hussein Borges, Chad R. |
| Author_xml | – sequence: 1 givenname: Hussein surname: Yassine fullname: Yassine, Hussein organization: Department of Medicine, University of Southern California, CA, Los Angeles, USA – sequence: 2 givenname: Chad R. surname: Borges fullname: Borges, Chad R. email: chad.borges@asu.edu organization: The Biodesign Institute, Arizona State University, AZ, Phoenix, USA – sequence: 3 givenname: Matthew R. surname: Schaab fullname: Schaab, Matthew R. organization: The Biodesign Institute, Arizona State University, AZ, Phoenix, USA – sequence: 4 givenname: Dean surname: Billheimer fullname: Billheimer, Dean organization: Southwest Environmental Health Sciences Center, University of Arizona, AZ, Tucson, USA – sequence: 5 givenname: Craig surname: Stump fullname: Stump, Craig organization: Department of Medicine, University of Arizona, Tucson, AZ, USA – sequence: 6 givenname: Peter surname: Reaven fullname: Reaven, Peter organization: Phoenix VA Health Care System, AZ, Phoenix, USA – sequence: 7 givenname: Serrine S. surname: Lau fullname: Lau, Serrine S. organization: Southwest Environmental Health Sciences Center, University of Arizona, Tucson, AZ, USA – sequence: 8 givenname: Randall surname: Nelson fullname: Nelson, Randall organization: The Biodesign Institute, Arizona State University, AZ, Phoenix, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23696124$$D View this record in MEDLINE/PubMed |
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| Snippet | 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... 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... 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... |
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| SubjectTerms | Amino Acid Sequence Apolipoprotein A-I Biomarkers - metabolism Blood Proteins - chemistry Blood Proteins - metabolism Cardiovascular disease Cardiovascular disease (CVD) Cardiovascular Diseases - blood Cardiovascular Diseases - metabolism Diabetes Diabetes Mellitus - blood Diabetes Mellitus - metabolism High density lipoprotein (HDL) Humans Immunoassay - methods Mass Spectrometry - methods Molecular Sequence Data Proteins |
| Title | Mass spectrometric immunoassay and MRM as targeted MS-based quantitative approaches in biomarker development: Potential applications to cardiovascular disease and diabetes |
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