Proteomics of heart disease...from molecular mechanisms to clinical diagnostics

Jennifer Van Eyk
Johns Hopkins University
Biomedical Engineering

Proteomics is the study of the proteome or the protein complement of a cell. It is the proteome that directly dictates the phenotype of the cell. In heart disease, the proteome of the cardiac myocytes undergo continuous and dynamic changes. The protein changes can be functionally benign, advantageous or detrimental but, collectively result in the disease phenotype.

Proteomics strives to characterize the proteome or a specific component of the proteome, a subproteome. Technically this is not trivial; it requires a number of sophisticated techniques in combination that involve protein separation, identification and characterization. Proteomics pushes the technical limits as it attempts to provide information to complete our understanding of how the cell, tissue, organ or in some cases the whole cardiovascular system adapts during disease. Of course, the changes to the proteome can also be protective, resulting in reduced cell death or infarction. With ischemic preconditioning, a potent means of myocyte protection, there are many proteome changes. Traditionally, preconditioning is induced through a brief transient ischemic event that prepares the cell against a more severe lethal event. Pharmacological agents, such as adenosine and diazoxide can also create protective measures that help the cell against further injury. We have found that treatment of either of these drugs produce many protein changes with the majority residing within the mitochondria.

Clinical proteomics is the application of proteomics specific to the field of medicine. It encompasses the translation of the proteomic technologies and methods into the production of diagnostics and therapeutics for the direct improvement to human health.
Development of serum based diagnostic markers involve a comprehensive strategy combining proteomic techniques in serum discovery as well as the validation of the potential biomarkers. An example is tracking and monitoring the disease-induced modifications of troponin I, the current gold standard for diagnosis of acute myocardial infarction. This has lead the way in applying knowledge obtained from discovery directly to a new level of diagnosis.


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