Role of inflammation in right ventricular damage and repair following experimental pulmonary embolism in rats

John Albert Watts, Michael Aaron Gellar, Maria Obraztsova, Jeffrey Allen Kline, John Zagorski

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Right ventricular (RV) dysfunction is associated with poor clinical outcome following pulmonary embolism (PE). Previous studies in our laboratory show that influx of neutrophils contributes to acute RV damage seen in an 18 h rat model of PE. The present study describes the further progression of inflammation over 6 weeks and compares the neutrophil and monocyte responses. The RV outflow tract became white in colour by day 1 with influx of neutrophils (tissue myeloperoxidase activity increased 17-fold) and mononuclear cells with characteristics of M1 phenotype (high in Ccl20, Cxcl10, CcR2, MHCII, DNA microarray analysis). Matrix metalloproteinase activities were increased and tissue was thinned to produce a translucent appearance in weeks 1 through 6 in 40% of hearts. RV contractile function was significantly reduced at 6 weeks of PE. In this later phase, there was accumulation of myofibroblasts, the presence of mononuclear cells with M2 characteristics (high in scavenger mannose receptors, macrophage galactose lectin 1, PDGFR1, PDGFRβ), enrichment of the subendocardial region of the RV outflow tract with neovesels (α-smooth muscle immunohistochemistry) and deposition of collagen fibres (picrosirius red staining) beginning scar formation. Thus, while neutrophil response is associated with the early, acute inflammatory events, macrophage cells continue to be present during the proliferative phase and initial deposition of collagen in this model, changing from the M1 to the M2 phenotype. This suggests that the macrophage cell response is biphasic.

Original languageEnglish (US)
Pages (from-to)389-399
Number of pages11
JournalInternational Journal of Experimental Pathology
Volume89
Issue number5
DOIs
StatePublished - Oct 1 2008
Externally publishedYes

Keywords

  • Healing
  • Inflammation
  • Macrophages
  • Neutrophils
  • Pulmonary embolism
  • Right ventricle

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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