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CARDIOVASCULAR GENOMIC MEDICINE

Cardiovascular Proteomics

Tools to Develop Novel Biomarkers and Potential Applications

Sara Arab, PhD^_*,¶, Anthony O. Gramolini, PhD^_*,,1, Peipei Ping, PhD^#, Thomas Kislinger, PhD^,, Brian Stanley, PhD^||,_**, Jennifer van Eyk, PhD^||,_**,2, Maral Ouzounian, MD^_*,||, David H. MacLennan, PhD^_*,,1, Andrew Emili, PhD^_*,,1 and Peter P. Liu, MD^_*,¶,1,_*

^_* Heart and Stroke/Richard Lewar Center of Excellence, University of Toronto and the Canadian Institutes of Health Research, Ottawa, Ontario, Canada
Department of Physiology, University of Toronto, Toronto, Ontario, Canada
Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada
Program in Proteomics and Bioinformatics, University of Toronto, Toronto, Ontario, Canada
^|| Queen’s University, Kingston, Ontario, Canada
^¶ Department of Medicine, University of Toronto, Toronto, Ontario, Canada
^# University of California Los Angeles–David Geffen School of Medicine, Los Angeles, California
^_** Johns Hopkins NHLBI Proteomics Center, Baltimore, Maryland.

Manuscript received February 9, 2006; revised manuscript received May 30, 2006, accepted June 5, 2006.

^_* Reprint requests and correspondence: Dr. Peter Liu, Heart & Stroke/Richard Lewar Centre of Excellence and Institute of Circulatory and Respiratory Health, Canadian Institute of Health Research, NCSB 11-1266, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada. (Email: peter.liu{at}utoronto.ca).

Proteomics is the new systems biological approach to the study of proteins and protein variation on a large scale as a result of biological processes and perturbations. The field is undergoing a dramatic transformation, owing to the completion and annotation of the human genome as well as technological advances to study proteins on a large scale. The new science of proteomics can potentially yield novel biomarkers reflecting cardiovascular disease, establish earlier detection strategies, and monitor responses to therapy. Technological advances permit the unprecedented large-scale identification of peptide sequences in a biological sample with mass spectrometry, whereas gel-based techniques provide further refinement on the status of post-translational modification. The application of high throughput protein evaluation with a subset of predefined targets, identified through proteomics, microarray profiling, and pathway analysis in animal models and human tissues, is gaining momentum in research and clinical applications. Proteomic analysis has provided important insights into ischemic heart disease, heart failure, and cardiovascular pathophysiology. The combination of proteomic biomarkers with clinical phenotypes and genetic haplotype information can lead to a more precise diagnosis and therapy on an individual basis—the fundamental premise of "personalized medicine."

Abbreviations and Acronyms   ELISA = enzyme-linked immunoadsorbent assay   HUPO = Human Proteomic Organisation   PTM = post-translational modification

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