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

Rahul Suresh, Xing Li, Anca Chiriac, Kashish Goel, Andre Terzic, Carmen Perez-Terzic, Timothy J. Nelson

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Background: Whole-genome gene expression analysis has been successfully utilized to diagnose, prognosticate, and identify potential therapeutic targets for high-risk cardiovascular diseases. However, the feasibility of this approach to identify outcome-related genes and dysregulated pathways following first-time myocardial infarction (AMI) remains unknown and may offer a novel strategy to detect affected expressome networks that predict long-term outcome. Methods and results: Whole-genome expression microarray on blood samples from normal cardiac function controls (n. = 21) and first-time AMI patients (n. = 31) within 48-hours post-MI revealed expected differential gene expression profiles enriched for inflammation and immune-response pathways. To determine molecular signatures at the time of AMI associated with 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 genes involved in the developmental epithelial-to-mesenchymal transition pathway, and 2) modulation of cholesterol transport genes that include ABCA1, CETP, APOA1, and LDLR is associated with clinical outcome. Conclusion: Differentially regulated genes and modulated pathways were identified that were associated with recurrent cardiovascular outcomes in first-time AMI patients. This cell-based approach for risk stratification in AMI could represent a novel, non-invasive platform to anticipate modifiable pathways and therapeutic targets to optimize long-term outcome for AMI patients and warrants further study to determine the role of metabolic remodeling and regenerative processes required for optimal outcomes.

Original languageEnglish (US)
Pages (from-to)13-21
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume74
DOIs
StatePublished - Sep 2014

Keywords

  • Acute myocardial infarction
  • Blood
  • Microarray
  • Pathway analysis
  • Transcriptome

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Transcriptome from circulating cells suggests dysregulated pathways associated with long-term recurrent events following first-time myocardial infarction'. Together they form a unique fingerprint.

  • Cite this