Transcriptional changes in right ventricular tissues are enriched in the outflow tract compared with the apex during chronic pulmonary embolism in rats

John Zagorski, Maria Obraztsova, Michael A. Gellar, Jeffrey A. Kline, John A. Watts

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Moderate to severe pulmonary embolism (PE) can cause pulmonary arterial hypertension and right ventricular (RV) heart damage. Previous studies from our laboratory indicate that the basal outflow tract of the RV is injured and has acute inflammation followed by tissue remodeling while the apex appears normal. The present studies examine transcription responses to chronic PE in RV apex and outflow tracts using DNA microarrays to identify transcription responses by region. Changes predominated in the RV outflow tract (8,575 genes showed ≥1.5-fold expression change). Gene ontology and KEGG analyses indicated a significant decrease in genes involved in cellular respiration and energy metabolism and increases in inflammatory cell adhesion molecules and extracellular matrix proteins. Signal pathways for wound healing such as fibroblast growth factor, collagen synthesis, and CCN proteins (named for the first three members of the family: cysteine-rich protein 61, connective tissue growth factor, and nephroblastoma overexpressed gene) were strongly upregulated. In comparison, few genes (422) showed significant change in the RV apex tissue. Apex-selective genes included two genes affecting metabolism and a stretch-sensitive transcription factor (ankyrin repeat domain 1). We conclude that the RV outflow tract is subject to strong proinflammatory and profibrotic remodeling transcriptional responses in chronic PE. Severe loss of genes involved in cellular respiration is consistent with previous histology indicating a shift in cell types present within the outflow tract tissue away from highly energydependant cardiomyocytes to less metabolically active cells during remodeling. The apex region of the RV had few compensating adaptations.

Original languageEnglish (US)
Pages (from-to)61-71
Number of pages11
JournalPhysiological Genomics
Volume39
Issue number1
DOIs
StatePublished - Sep 1 2009
Externally publishedYes

Keywords

  • Heart
  • Inflammation
  • Microarray
  • Pulmonary hypertension
  • Wnt signaling

ASJC Scopus subject areas

  • Physiology
  • Genetics

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