Increased immunoreactive endothelin-1 in human transplant coronary artery disease.
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.


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.
Ravalli
S
S
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Szabolcs
M
M
Albala
A
A
Michler
R E
RE
Cannon
P J
PJ
D000328:Adult; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D003327:Coronary Disease / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D003331:Coronary Vessels / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D019332:Endothelin-1 / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous
D019332:Endothelin-1