Inducible nitric oxide synthase expression in smooth muscle cells and macrophages of human transplant coronary artery disease

Stefano Ravalli, Arline Albala, Ming Ming, Matthias Szabolcs, Alessandro Barbone, Robert E. Michler, Paul J. Cannon

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Background - The inducible isoform of the nitric oxide synthase (iNOS) produces large amounts of nitric oxide in response to cytokine stimulation. Previous investigations have demonstrated iNOS expression in the setting of acute and chronic rejection in experimental cardiac transplant models. The goal of this study was to investigate whether iNOS is upregulated in human transplant coronary artery disease (TCAD), a major cause of late mortality after cardiac transplantation. Methods and Results - We studied 15 patients with TCAD and 10 with normal coronary arteries. In situ hybridization and immunohistochemistry were used in tissue sections to localize iNOS mRNA and protein, respectively. The presence of peroxynitrite was indirectly assessed by immunostaining with an anti-nitrotyrosine antibody. Normal coronary arteries had no evidence of iNOS expression. In contrast, 30 of 36 coronary artery segments with TCAD (83%) were immunostained by the iNOS antibody. The presence of iNOS mRNA was demonstrated in these vessels by in situ hybridization. Specific cell markers identified iNOS-positive cells as neointimal macrophages and smooth muscle cells. Conclusions - iNOS mRNA-and protein are expressed in human arteries with TCAD, where they are associated with extensive nitration on protein tyrosines. These findings indicate that the high-output nitric oxide pathway and possibly the oxidant peroxynitrite might be involved in the process leading to the development of TCAD.

Original languageEnglish (US)
Pages (from-to)2338-2345
Number of pages8
JournalCirculation
Volume97
Issue number23
DOIs
StatePublished - Jun 16 1998
Externally publishedYes

Keywords

  • Arteriosclerosis
  • Endothelium-derived factors
  • Transplantation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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