Increased immunoreactive endothelin-1 in human transplant coronary artery disease

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

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Background: The pathogenesis of transplant coronary artery disease (TCAD) is unknown, but it is thought to derive from an interaction between immune and nonimmune factors, leading to smooth muscle cell proliferation and accumulation in the expanded neointima. Endothelin-1 (ET-1), a potent vasoconstrictor with mitogenic properties for vascular smooth muscle cells, has recently been demonstrated in native vessel atherosclerosis. The present study used immunohistochemistry to investigate the role of ET-1 in TCAD. Methods and Results: ET-1 immunoreactivity and cellular localization were assessed in human coronary arteries with TCAD (n=13) and in normal coronary arteries (n=10) with single- and double-label immunohistochemistry. The intensity of immunostaining was determined by a semiquantitative method. Diffuse and intense ET-1 immunoreactivity was found in 11 of 13 patients with TCAD (85%), mainly in myointimal cells and, in lesser amounts, in macrophages and endothelial cells. In contrast, normal coronary arteries had only faint immunostaining localized to the endothelial layer. Mean semiquantitative grade was significantly higher in TCAD than in normal arteries (1.8 versus 0.7; P<.05). ET-1 was more frequently present in lipid-rich, atheromatous lesions than in lipid-poor, proliferative ones. Intimal neovessels consistently immunostained for ET-1. Conclusions: Immunoreactivity for ET-1 is significantly increased in TCAD, possibly as a result of stimulatory cytokines and growth factors that are upregulated in the posttransplant state. The results suggest a role for this mitogenic peptide in the pathogenesis of graft arteriosclerosis.

Original languageEnglish (US)
Pages (from-to)2096-2102
Number of pages7
Issue number9
StatePublished - 1996
Externally publishedYes


  • arteriosclerosis
  • endothelin
  • transplantation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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