| Myocardial infarction (MI) is a major cause of morbidityand mortality worldwide, with approximately 500,000-700,000 deaths caused by ischemic heart disease in theUnited States each year. The causes of the disease havebeen well-established, but the build-up to a massive heartattack is difficult to predict, particularly during earlystages of disease progression when prevention is stillpossible. Proteomics – both large-scale protein identifi-cation and quantitative differential expression – may beused to identify improved diagnostic markers and contributeto our understanding of biochemical pathwaystriggered during myocardial injury that might one dayserve as targets for drug therapy.
In this study, samples were obtained in a time-coursefashion from patients undergoing alcohol septal ablationfor hypertrophic cardiomyopathy (a “planned” myocardialinfarction) and analyzed in triplicate to track changesin their protein profile during the course of treatment.Bottom-up proteomics analysis was accomplished in twosteps, namely (1) off-line fractionation by strong anionexchange chromatography (SAX) of plasma proteins inorder to circumvent the need for depletion of high-abundanceproteins (e.g., albumin, IgG), followed by (2) replicatebottom-up analysis of digested fractions, by nanosprayLC/MSn with a Finnigan LTQ linear ion trap mass spectrometer,to assess semi-quantitative changes in the proteinprofile over the course of the planned MI.
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