Lipid overload and proteoglycan expression in chronic rejection of the human transplanted heart

B. M. McManus, G. Malcom, T. J. Kendall, J. M. Gulizia, J. E. Wilson, G. Winters, M. R. Costanzo, S. Thieszen, S. J. Radio

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Abstract

The degree to which transplant arteriopathy in solid organ allografts is an atheromatous process remains somewhat controversial. If atheromata develop as common and integral components of the arteriopathic lesions, then the process may be approached therapeutically in a manner analogous to native atheromatous diseases. Approaches to understanding the arteriopathic process may include not only the modulation of alloimmunity, but also the interruption of 'storage' phenomena. We have examined the epicardial coronary arteries of nearly 50 explanted human heart allografts using biochemical, morphological, morphometrical, immunohistochemical, and molecular techniques in an effort to establish the degree, nature, and distribution of lipid accumulation in the vessel walls. Concomitantly, we studied the ascertainment of proteoglycan gene expression, represented by biglycan and decorin messenger RNA, and the localization of proteoglycan proteins in the vessels. The degree of lipid and proteoglycan buildup in both the intima and media of transplanted vessels is striking, and correlated strongly with intimal thickening, cross-sectional area reduction of the lumen, cumulative cyclosporine dose, corticosteroid dose, and serum cholesterol levels. Notably, lipid accumulation is not related to implant duration, this being true in an unselected series of 'failed' allografts ranging from 4 to 1610 days post-transplant. The profound lipid accumulation in coronary walls of many grafts begins very early post-transplant and appears to contribute substantially to intimal thickening. Whether dysregulation of proteoglycan production leads to entrapment of lipids and lipoproteins remains an important and testable hypothesis.

Original languageEnglish (US)
Pages (from-to)336-340
Number of pages5
JournalClinical Transplantation
Volume8
Issue number3 II
Publication statusPublished - Jun 14 1994

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Keywords

  • Atherosclerosis
  • Endothelium
  • Graft rejection
  • Heart transplantation
  • Immunosuppression
  • Lipoprotein
  • Proteoglycans

ASJC Scopus subject areas

  • Transplantation

Cite this

McManus, B. M., Malcom, G., Kendall, T. J., Gulizia, J. M., Wilson, J. E., Winters, G., ... Radio, S. J. (1994). Lipid overload and proteoglycan expression in chronic rejection of the human transplanted heart. Clinical Transplantation, 8(3 II), 336-340.