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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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
StatePublished - Jun 14 1994

Fingerprint

Proteoglycans
Lipids
Tunica Intima
Allografts
Transplants
Biglycan
Decorin
Atherosclerotic Plaques
Cyclosporine
Lipoproteins
Coronary Vessels
Adrenal Cortex Hormones
Cholesterol
Gene Expression
Messenger RNA
Serum
Proteins

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.

Lipid overload and proteoglycan expression in chronic rejection of the human transplanted heart. / McManus, B. M.; Malcom, G.; Kendall, T. J.; Gulizia, J. M.; Wilson, J. E.; Winters, G.; Costanzo, M. R.; Thieszen, S.; Radio, S. J.

In: Clinical Transplantation, Vol. 8, No. 3 II, 14.06.1994, p. 336-340.

Research output: Contribution to journalArticle

McManus, BM, Malcom, G, Kendall, TJ, Gulizia, JM, Wilson, JE, Winters, G, Costanzo, MR, Thieszen, S & Radio, SJ 1994, 'Lipid overload and proteoglycan expression in chronic rejection of the human transplanted heart', Clinical Transplantation, vol. 8, no. 3 II, pp. 336-340.
McManus BM, Malcom G, Kendall TJ, Gulizia JM, Wilson JE, Winters G et al. Lipid overload and proteoglycan expression in chronic rejection of the human transplanted heart. Clinical Transplantation. 1994 Jun 14;8(3 II):336-340.
McManus, B. M. ; Malcom, G. ; Kendall, T. J. ; Gulizia, J. M. ; Wilson, J. E. ; Winters, G. ; Costanzo, M. R. ; Thieszen, S. ; Radio, S. J. / Lipid overload and proteoglycan expression in chronic rejection of the human transplanted heart. In: Clinical Transplantation. 1994 ; Vol. 8, No. 3 II. pp. 336-340.
@article{c75a0743ecd64649b8b40e39de3eed7f,
title = "Lipid overload and proteoglycan expression in chronic rejection of the human transplanted heart",
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.",
keywords = "Atherosclerosis, Endothelium, Graft rejection, Heart transplantation, Immunosuppression, Lipoprotein, Proteoglycans",
author = "McManus, {B. M.} and G. Malcom and Kendall, {T. J.} and Gulizia, {J. M.} and Wilson, {J. E.} and G. Winters and Costanzo, {M. R.} and S. Thieszen and Radio, {S. J.}",
year = "1994",
month = "6",
day = "14",
language = "English (US)",
volume = "8",
pages = "336--340",
journal = "Clinical Transplantation",
issn = "0902-0063",
publisher = "Wiley-Blackwell",
number = "3 II",

}

TY - JOUR

T1 - Lipid overload and proteoglycan expression in chronic rejection of the human transplanted heart

AU - McManus, B. M.

AU - Malcom, G.

AU - Kendall, T. J.

AU - Gulizia, J. M.

AU - Wilson, J. E.

AU - Winters, G.

AU - Costanzo, M. R.

AU - Thieszen, S.

AU - Radio, S. J.

PY - 1994/6/14

Y1 - 1994/6/14

N2 - 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.

AB - 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.

KW - Atherosclerosis

KW - Endothelium

KW - Graft rejection

KW - Heart transplantation

KW - Immunosuppression

KW - Lipoprotein

KW - Proteoglycans

UR - http://www.scopus.com/inward/record.url?scp=0028303764&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028303764&partnerID=8YFLogxK

M3 - Article

C2 - 8061377

AN - SCOPUS:0028303764

VL - 8

SP - 336

EP - 340

JO - Clinical Transplantation

JF - Clinical Transplantation

SN - 0902-0063

IS - 3 II

ER -