|Publication Type||Journal Article|
|Year of Publication||2010|
|Authors||Gerszten, RE, Carr, SA, Sabatine, M|
|Date Published||2010 Feb|
|Keywords||Biomarkers, Humans, Interleukin-33, Interleukins, Myocardial Infarction, Proteomics, Tandem Mass Spectrometry, Troponin I|
BACKGROUND: Given the mounting evidence in favor of early pharmacologic and catheter-based interventions for patients across the spectrum of acute coronary syndromes, discovering novel diagnostically sensitive and specific biomarkers that provide biochemical proof of early or reversible myocardial injury could have a substantial positive impact on patient care.
CONTENT: To address unmet needs in disease biomarkers, investigators have turned to proteomics approaches. We describe advances in proteomics discovery technologies based on liquid chromatography-tandem mass spectrometry that facilitate the unbiased analysis of low-abundance blood proteins. We detail the development of emerging techniques to enhance the biomarker verification process, such as accurate inclusion mass screening, stable isotope dilution-multiple reaction monitoring-mass spectrometry (SID-MRM-MS), and stable isotope standards with capture by antipeptide antibodies, which combines the advantages of specific immunoaffinity enrichment of a target peptide with the structural specificity and quantitative capabilities of SID-MRM-MS. We highlight new assays incorporating these techniques for troponin I, a representative low-abundance cardiac biomarker, and interleukin-33, an emerging novel marker of myocardial stress for which no existing ELISA exists. We demonstrate that troponin I and interleukin-33 peptides have a linear, dynamic range spanning 4 orders of magnitude and limits of detection of approximately 0.5 microg/L back-calculated to the protein concentration.
CONCLUSIONS: There remain important unmet diagnostic and prognostic needs in cardiology. Advances in technology may allow proteomics to play a vital role in the discovery and validation of novel biomarkers to help fill those needs.
|Alternate Journal||Clin. Chem.|
|Grant List||R01 HL096738-01 / HL / NHLBI NIH HHS / United States |
U24 CA126476 / CA / NCI NIH HHS / United States