(Circulation. 1996;94:2096-2102.)
© 1996 American Heart Association, Inc.
Articles |
Increased Immunoreactive Endothelin-1 in Human Transplant Coronary Artery Disease
the Departments of Medicine, Division of Cardiology (S.R., A.A., P.J.C.); Pathology (M.S.); and Surgery, Division of Cardiothoracic Surgery (R.E.M.), Columbia University College of Physicians and Surgeons, New York, NY.
Correspondence to Paul J. Cannon, MD, Division of Cardiology, Columbia University College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032.
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.
Key Words: arteriosclerosis • transplantation • endothelin
This article has been cited by other articles:
 |
|
 |
|
  D. Ramzy, V. Rao, L. C. Tumiati, N. Xu, R. Sheshgiri, S. Miriuka, D. H. Delgado, and H. J. Ross Elevated Endothelin-1 Levels Impair Nitric Oxide Homeostasis Through a PKC-Dependent Pathway Circulation, July 4, 2006; 114(1_suppl): I-319 - I-326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. W.M. Fedak, V. Rao, S. Verma, D. Ramzy, L. Tumiati, S. Miriuka, P. Boylen, R. D. Weisel, and C. M. Feindel Combined endothelial and myocardial protection by endothelin antagonism enhances transplant allograft preservation J. Thorac. Cardiovasc. Surg., February 1, 2005; 129(2): 407 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Vassalli, A. Gallino, M. Weis, W. von Scheidt, L. Kappenberger, L.K. von Segesser, J.-J. Goy, and on behalf of the Working Group Microcirculation of Alloimmunity and nonimmunologic risk factors in cardiac allograft vasculopathy Eur. Heart J., July 1, 2003; 24(13): 1180 - 1188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Weis and J. P. Cooke Cardiac Allograft Vasculopathy and Dysregulation of the NO Synthase Pathway Arterioscler. Thromb. Vasc. Biol., April 1, 2003; 23(4): 567 - 575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Orth, G. Odoni, H. Karkoszka, H. Ogata, C. Viedt, K. Amann, P. Ferrari, and E. Ritz Combination treatment with an ETA-receptor blocker and an ACE inhibitor is not superior to the respective monotherapies in attenuating chronic transplant vasculopathy in different aorta allotransplantation rat models Nephrol. Dial. Transplant., January 1, 2003; 18(1): 62 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Adams, G. Odoni, H. Ogata, C. Viedt, K. Amann, E. Ritz, and S. R. Orth Combination treatment with an ETA-receptor blocker and an ACE inhibitor is not superior to the respective monotherapies in attenuating chronic transplant nephropathy in a 'Fisher-to-Lewis' rat model Nephrol. Dial. Transplant., May 1, 2002; 17(5): 780 - 787. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K. Sihvola, V. P. Pulkkinen, P. K. Koskinen, and K. B. Lemstrom Crosstalk of endothelin-1 and platelet-derived growth factor in cardiac allograft arteriosclerosis J. Am. Coll. Cardiol., February 20, 2002; 39(4): 710 - 717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Berkenboom, V. Crasset, and P. Unger Coronary endothelial dysfunction in the early months after heart transplantation J. Am. Coll. Cardiol., March 1, 2001; 37(3): 969 - 969. [Full Text] [PDF]
|
|
|
|
|
|
T. F. Luscher and M. Barton Endothelins and Endothelin Receptor Antagonists : Therapeutic Considerations for a Novel Class of Cardiovascular Drugs Circulation, November 7, 2000; 102(19): 2434 - 2440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Eisenberg, H. J. Chen, M. K. Warshofsky, R. R. Sciacca, H. S. Wasserman, A. Schwartz, and L. E. Rabbani Elevated Levels of Plasma C-Reactive Protein Are Associated With Decreased Graft Survival in Cardiac Transplant Recipients Circulation, October 24, 2000; 102(17): 2100 - 2104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Aziz, P. Hasleton, A. W. Hann, N. Yonan, A. Deiraniya, and I. V. Hutchinson TRANSFORMING GROWTH FACTOR {beta} IN RELATION TO CARDIAC ALLOGRAFT VASCULOPATHY AFTER HEART TRANSPLANTATION J. Thorac. Cardiovasc. Surg., April 1, 2000; 119(4): 700 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Gilbert, J. R. Rumble, Z. Cao, A. J. Cox, P. van Eeden, T. J. Allen, D. J. Kelly, and M. E. Cooper Endothelin Receptor Antagonism Ameliorates Mast Cell Infiltration, Vascular Hypertrophy, and Epidermal Growth Factor Expression in Experimental Diabetes Circ. Res., February 4, 2000; 86(2): 158 - 165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Iwasaki, S. Eguchi, H. Ueno, F. Marumo, and Y. Hirata Endothelin-Mediated Vascular Growth Requires p42/p44 Mitogen-Activated Protein Kinase and p70 S6 Kinase Cascades via Transactivation of Epidermal Growth Factor Receptor Endocrinology, October 1, 1999; 140(10): 4659 - 4668. [Abstract] [Full Text]
|
|
|
|
|
|
G. P. Rossi, S. Colonna, E. Pavan, G. Albertin, F. Della Rocca, G. Gerosa, D. Casarotto, S. Sartore, P. Pauletto, and A. C. Pessina Endothelin-1 and Its mRNA in the Wall Layers of Human Arteries Ex Vivo Circulation, March 9, 1999; 99(9): 1147 - 1155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Geny, G. Brandenberger, J. Lonsdorfer, N. Chakfe, P. Haberey, and F. Piquard Circulating adrenomedullin is increased after heart transplantation Cardiovasc Res, March 1, 1999; 41(3): 731 - 736. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. ORTH, G. ODONI, K. AMANN, P. STRZELCZYK, M. RASCHACK, and E. RITZ The ETA Receptor Blocker LU 135252 Prevents Chronic Transplant Nephropathy in the "Fisher to Lewis" Model J. Am. Soc. Nephrol., February 1, 1999; 10(2): 387 - 391. [Abstract] [Full Text]
|
|
|
|
|
|
B. Geny, F. Piquard, J. Lonsdorfer, and P. Haberey Endothelin and heart transplantation Cardiovasc Res, September 1, 1998; 39(3): 556 - 562. [Full Text] [PDF]
|
|
|
|
|
|
K. Okada, Y. Nishida, H. Murakami, I. Sugimoto, H. Kosaka, H. Morita, C. Yamashita, and M. Okada Role of Endogenous Endothelin in the Development of Graft Arteriosclerosis in Rat Cardiac Allografts : Antiproliferative Effects of Bosentan, a Nonselective Endothelin Receptor Antagonist Circulation, June 16, 1998; 97(23): 2346 - 2351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Ferri, G. Properzi, G. Tomassoni, A. Santucci, G. Desideri, A. E. Giuliani, R. C. Starling, N. B. Ratliff, D. J. Cook, P. McCarthy, et al. Patterns of Myocardial Endothelin-1 Expression and Outcome After Cardiac Transplantation Circulation, April 16, 2002; 105(15): 1768 - 1771. [Abstract] [Full Text] [PDF]
|
|