title: Targeted quantitation of CVD-linked plasma proteins for biomarker verification and validation.
abstract: Despite significant advances in treatment, cardiovascular disease (CVD) remains one of the leading causes of morbidity and mortality in developed and developing countries. Judicious monitoring of common risk factors has been unable to control this global epidemic, necessitating novel biomarkers for improved screening and earlier disease detection and management. Although numerous plasma proteins have been associated with CVD, only a few of these potential biomarkers have been validated for clinical use. Here we review the quantitative proteomic methods used to verify and validate new biomarker candidates in human plasma. These methods center on a bottom-up approach involving multiple or selected reaction monitoring, for targeted detection, with stable isotope-labeled standards, for peptide normalization. Also included are a discussion of future strategies for improved CVD protein biomarker verification and validation, recommendations for method translation to the clinic, and future projections for protein biomarker research.
authors.affiliation: University of Victoria - Genome British Columbia Proteomics Centre, Vancouver Island Technology Park, #3101 - 4464 Markham St., Victoria, BC V8Z 7X8, Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Percy
authors.forename: Simon
authors.initials: S
authors.lastname: Byrns
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Chambers
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Borchers
mesh_terms: D015415:Biomarkers / Q000032:analysis; D001798:Blood Proteins / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D040901:Proteomics / Q000379:methods*; D054928:Validation Studies as Topic
chemical_list: D015415:Biomarkers; D001798:Blood Proteins