Abstract
Different methodologies have been used through years to discover new potential biomarkers related with cardiovascular risk. The conventional proteomic strategy involves a discovery phase that requires the use of mass spectrometry (MS) and a validation phase, usually on an alternative platform such as immunoassays that can be further implemented in clinical practice. This approach is suitable for a single biomarker, but when large panels of biomarkers must be validated, the process becomes inefficient and costly. Therefore, it is essential to find an alternative methodology to perform the biomarker discovery, validation, and quantification. The skills provided by quantitative MS turn it into an extremely attractive alternative to antibody-based technologies. Although it has been traditionally used for quantification of small molecules in clinical chemistry, MRM is now emerging as an alternative to traditional immunoassays for candidate protein biomarker validation.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
McGregor E, Dunn MJ (2003) Proteomics of heart disease. Hum Mol Genet 12(Spec No. 2):R135–R144
Van Eyk JE, Dunn MJ (2003) Proteomic and genomic analysis of cardiovascular disease. Wiley, Chichester
Mayr M, Mayr U, Chung YL, Yin X, Griffiths JR, Xu Q (2004) Vascular proteomics: linking proteomic and metabolomic changes. Proteomics 4:3751–3761
Marian AJ, Nambi V (2004) Biomarkers of cardiac disease. Expert Rev Mol Diagn 4:805–820
Barderas MG, Tunon J, Darde VM, De la Cuesta F, Duran MC, Jiménez-Nácher JJ, Tarín N, López-Bescós L, Egido J, Vivanco F (2007) Circulating human monocytes in the acute coronary syndrome express a characteristic proteomic profile. J Proteome Res 6:876–886
Darde VM, De la Cuesta F, Gil-Dones F, Alvarez-Llamas G, Barderas MG, Vivanco F (2010) Analysis of the plasma proteome associated with acute coronary syndrome: does a permanent protein signature exist in the plasma of ACS patients? J Proteome Res 9:4420–4432
Gil-Dones F, Martin-Rojas T, Lopez-Almodovar LF, de la Cuesta F, Darde VM, Alvarez-Llamas G, Juarez-Tosina R, Barroso G, Vivanco F, Padial LR, Barderas MG (2010) Valvular aortic stenosis: a proteomic insight. Clin Med Insights Cardiol 4:1–7
Rifai N, Gillette MA, Carr SA (2006) Protein biomarker discovery and validation: the long and uncertain path to clinical utility. Nat Biotechnol 24:971–983
Perchalski R, Yost R, Wilder B (1982) Structural elucidation of drug metabolites by triple-quadrupole mass spectrometry. Anal Chem 54:1466–1471
Tiller PR, Cunniff J, Land AP, Schwartz J, Jardine I, Wakefield M, Lopez L, Newton JF, Burton RD, Folk BM, Buhrman DL, Price P, Wu D (1997) Drug quantitation on a benchtop liquid chromatography-tandem mass spectrometry system. J Chromatogr A 771:119–125
Lee MS, Kerns EH (1999) LC/MS applications in drug development. Mass Spectrom Rev 18:187–279
Tai SS, Bunk DM, White ET, Welch MJ (2004) Development and evaluation of a reference measurement procedure for the determination of total 3,3,5-triiodothyronine in human serum using isotope-dilution liquid chromatography-tandem mass spectrometry. Anal Chem 76:5092–5096
Sannino A, Bolzoni L, Bandini M (2004) Application of liquid chromatography with electrospray tandem mass spectrometry to the determination of a new generation of pesticides in processed fruits and vegetables. J Chromatogr A 1036:161–169
Keshishian H, Addona T, Burgess M, Kuhn E, Carr SA (2007) Quantitative, multiplexed assays for low abundance proteins in plasma by targeted mass spectrometry and stable isotope dilution. Mol Cell Proteomics 6:2212–2229
Barr DB, Barr JR, Maggio VL, Whitehead RD Jr, Sadowski MA, Whyatt RM, Needham LL (2002) A multi-analyte method for the quantification of contemporary pesticides in human serum and plasma using high-resolution mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 778:99–111
Keshishian H, Addona T, Burgess M, Mani DR, Shi X, Kuhn E, Sabatine MS, Gerszten RE, Carr SA (2009) Quantification of cardiovascular biomarkers in patient plasma by targeted mass spectrometry and stable isotope dilution. Mol Cell Proteomics 8:2339–2349
Kuhn E, Wu J, Karl J, Liao H, Zolg W, Guild B (2004) Quantification of C-reactive protein in the serum of patients with rheumatoid arthritis using multiple reaction monitoring mass spectrometry and 13C labeled peptide standards. Proteomics 4:1175–1186
Gil-Dones F, Darde VM, Alonso-Orgaz S, Lopez-Almodovar LF, Mourino-Alvarez L, Padial LR, Vivanco F, Barderas MG (2012) Inside human aortic stenosis: a proteomic analysis of plasma. J Proteomics 75:1639–1653
Hager JW (2002) A new linear ion trap mass spectrometer. Rapid Commun Mass Spectrom 16:512–526
Hopfgartner G, Varesio E, Tschappat V, Grivat C, Bourgogne E, Leuthold LA (2004) Triple quadrupole linear ion trap mass spectrometer for the analysis of small molecules and macromolecules. J Mass Spectrom 39:845–855
Unwin RD, Griffiths JR, Leverentz MK, Grallert A, Hagan IM, Whetton AD (2005) Multiple reaction monitoring to identify sites of protein phosphorylation with high sensitivity. Mol Cell Proteomics 4:1134–1144
Acknowledgments
This work was supported by grants from FIS PI11/01401 and FIS PI08/0970 and by SESCAM.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this protocol
Cite this protocol
Dardé, V.M., Barderas, M.G., Vivanco, F. (2013). Multiple Reaction Monitoring (MRM) of Plasma Proteins in Cardiovascular Proteomics. In: Vivanco, F. (eds) Vascular Proteomics. Methods in Molecular Biology, vol 1000. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-405-0_14
Download citation
DOI: https://doi.org/10.1007/978-1-62703-405-0_14
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-404-3
Online ISBN: 978-1-62703-405-0
eBook Packages: Springer Protocols