Transcriptome from circulating cells suggests dysregulated pathways associated with long-term recurrent events following first-time myocardial infarction.

Whole-genome microarray and targeted cytokine expression profiling on blood samples from normal cardiac function controls and first-time AMI patients within 48-hours post-MI revealed expected differential gene expression profiles enriched for inflammation and immune-response pathways in AMI patients. To determine molecular signatures at the time of AMI that could prognosticate long-term outcomes, transcriptional profiles from sub-groups of AMI patients with (n=5) or without (n=22) any recurrent events over an 18-month follow-up were compared. This analysis identified 559 differentially expressed genes. Bioinformatic analysis of this differential gene set for associated pathways revealed 1) increasing disease severity in AMI patients is associated with a decreased expression of the developmental epithelial-to-mesenchymal transition, and 2) modulation of cholesterol transport genes that include ABCA1, CETP, APOA1, and LDLR is associated with clinical outcome. In conclusion, differentially regulated genes and modulated pathways were identified that predicted recurrent cardiovascular outcomes in first-time AMI patients. This cell-based approach for risk stratification in AMI warrants a larger study to determine the role of metabolic remodeling and regenerative processes required for optimal outcomes. A validated transcriptome assay could represent a novel, non-invasive platform to anticipate modifiable pathways and therapeutic targets to optimize long-term outcome for AMI patients.