Identification of temporal and region-specific myocardial gene expression patterns in response to infarction in swine

PLoS One. 2013;8(1):e54785. doi: 10.1371/journal.pone.0054785. Epub 2013 Jan 25.

Abstract

Molecular mechanisms associated with pathophysiological changes in ventricular remodelling due to myocardial infarction (MI) remain poorly understood. We analyzed changes in gene expression by microarray technology in porcine myocardial tissue at 1, 4, and 6 weeks post-MI.MI was induced by coronary artery ligation in 9 female pigs (30-40 kg). Animals were randomly sacrificed at 1, 4, or 6 weeks post-MI (n = 3 per group) and 3 healthy animals were also included as control group. Total RNA from myocardial samples was hybridized to GeneChip® Porcine Genome Arrays. Functional analysis was obtained with the Ingenuity Pathway Analysis (IPA) online tool. Validation of microarray data was performed by quantitative real-time PCR (qRT-PCR).More than 8,000 different probe sets showed altered expression in the remodelling myocardium at 1, 4, or 6 weeks post-MI. Ninety-seven percent of altered transcripts were detected in the infarct core and 255 probe sets were differentially expressed in the remote myocardium. Functional analysis revealed 28 genes de-regulated in the remote myocardial region in at least one of the three temporal analyzed stages, including genes associated with heart failure (HF), systemic sclerosis and coronary artery disease. In the infarct core tissue, eight major time-dependent gene expression patterns were recognized among 4,221 probe sets commonly altered over time. Altered gene expression of ACVR2B, BID, BMP2, BMPR1A, LMNA, NFKBIA, SMAD1, TGFB3, TNFRSF1A, and TP53 were further validated.The clustering of similar expression patterns for gene products with related function revealed molecular footprints, some of them described for the first time, which elucidate changes in biological processes at different stages after MI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cluster Analysis
  • Disease Models, Animal
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation*
  • Gene Regulatory Networks
  • Myocardial Infarction / genetics*
  • Myocardium / metabolism*
  • Myocardium / pathology*
  • Reproducibility of Results
  • Signal Transduction
  • Swine
  • Time Factors

Associated data

  • GEO/GSE34569

Grants and funding

This work was supported by the Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Sara Borrell Grant (CD07/00163 to CP-V), Ministerio de Ciencia e Innovación (SAF2008-05144-C02-01 and SAF2011-30067-C02-01 to AB-G), Fundació Privada Daniel Bravo Andreu, and La Marató de TV3 (080330 to AB-G). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.