Endothelin-1 immunoreactivity and mRNA in the transplanted human heart

A. Giaid, D. Saleh, Masashi Yanagisawa, R. D C Forbes

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Abstract

Endothelin-1 (ET-1) is a 21-residue peptide produced by endothelial cells and possesses a wide range of biological activities, including vasoconstriction, mito-genesis, and inotropic effects on the heart. The aim of the present study was to determine the cellular localization of ET-1 immunoreactivity and mRNA in routine endomyocardial biopsy specimens of transplanted human hearts, and to correlate the findings with the associated histological changes. Multiple-step paraffin sections of 72 biopsy samples were im-munostained with antiserum to ET-1 and von Will-ebrand factor (factor VIII) using the avidin-biotin-peroxidase complex method. ET-1 immunoreactivity was localized to vascular and endocardial endothelial cells, as well as to cardiomyocytes. The pattern of endothelial cell immunostaining with the ET-1 antiserum was similar to that of factor VIII. Previous biopsy sites and areas of granulation tissue appeared to have greater ET-1 immunoreactivity, particularly in sections immunostained with the ET-1 antiserum. There was a significant correlation between the presence of ET-1 immunoreactivity and fibrosis or granulation tissue in the biopsy specimens (P<0.03). There was no correlation between ET-1 immunoreactivity and the presence of cellular infiltrate, definitive rejection, or Quilty effect. In situ hybridization with radio-labeled RNA probes revealed expression of ET-1 mRNA in endothelial cells and myocytes, also in association with granulation tissue and fibrosis. No cellular reactivity was present in control sections stained with the ET-1 antiserum preadsorped with its synthetic peptide. The findings suggests a possible role for ET-1 in vascular regeneration and angiogenesis following myocardial injury.

Original languageEnglish (US)
Pages (from-to)1308-1313
Number of pages6
JournalTransplantation
Volume59
Issue number9
StatePublished - May 15 1995

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ASJC Scopus subject areas

  • Transplantation

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Giaid, A., Saleh, D., Yanagisawa, M., & Forbes, R. D. C. (1995). Endothelin-1 immunoreactivity and mRNA in the transplanted human heart. Transplantation, 59(9), 1308-1313.