Apoptosis and cellular activation in the pathogenesis of acute vascular rejection

Zoie E. Holzknecht, Karisha L. Kuypers, Timothy B. Plummer, Josie Williams, Matilda Bustos, Gregory James Gores, Gregory J. Brunn, Jeffrey L. Platt

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Acute vascular or humoral rejection, a vexing outcome of organ transplantation, has been attributed by some to activation and by others to apoptosis of endothelial cells in the graft. We asked which of these processes causes acute vascular rejection by tracing the processes during the development of acute vascular rejection in porcine cardiac xenografts performed in baboons. Apoptosis, assayed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), expression of activated caspase-3, and proapoptotic genes Bax and Bcl-xL, was not detected until acute vascular rejection was well advanced, and even then, apoptosis was largely confined to myocytes. Activation of the endothelium, as evidenced by expansion of rough endoplasmic reticulum and increased ribosomal antigen and phospho-p70 S6 kinase, occurred early in the course of acute vascular rejection and progressed through the disease process. These findings suggest that acute vascular rejection is caused by an active metabolic process and not by apoptosis in the endothelium.

Original languageEnglish (US)
Pages (from-to)1135-1141
Number of pages7
JournalCirculation Research
Volume91
Issue number12
DOIs
StatePublished - Dec 2002

Fingerprint

Blood Vessels
Apoptosis
Endothelium
70-kDa Ribosomal Protein S6 Kinases
DNA Nucleotidylexotransferase
Rough Endoplasmic Reticulum
Papio
Organ Transplantation
Heterografts
Caspase 3
Muscle Cells
Swine
Endothelial Cells
Transplants
Antigens
Genes

Keywords

  • Apoptosis
  • Cardiac transplantation
  • Endothelial cells
  • Xenotransplantation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Holzknecht, Z. E., Kuypers, K. L., Plummer, T. B., Williams, J., Bustos, M., Gores, G. J., ... Platt, J. L. (2002). Apoptosis and cellular activation in the pathogenesis of acute vascular rejection. Circulation Research, 91(12), 1135-1141. https://doi.org/10.1161/01.RES.0000046236.20251.FA

Apoptosis and cellular activation in the pathogenesis of acute vascular rejection. / Holzknecht, Zoie E.; Kuypers, Karisha L.; Plummer, Timothy B.; Williams, Josie; Bustos, Matilda; Gores, Gregory James; Brunn, Gregory J.; Platt, Jeffrey L.

In: Circulation Research, Vol. 91, No. 12, 12.2002, p. 1135-1141.

Research output: Contribution to journalArticle

Holzknecht, ZE, Kuypers, KL, Plummer, TB, Williams, J, Bustos, M, Gores, GJ, Brunn, GJ & Platt, JL 2002, 'Apoptosis and cellular activation in the pathogenesis of acute vascular rejection', Circulation Research, vol. 91, no. 12, pp. 1135-1141. https://doi.org/10.1161/01.RES.0000046236.20251.FA
Holzknecht, Zoie E. ; Kuypers, Karisha L. ; Plummer, Timothy B. ; Williams, Josie ; Bustos, Matilda ; Gores, Gregory James ; Brunn, Gregory J. ; Platt, Jeffrey L. / Apoptosis and cellular activation in the pathogenesis of acute vascular rejection. In: Circulation Research. 2002 ; Vol. 91, No. 12. pp. 1135-1141.
@article{d84b258211e145d783909f6371575940,
title = "Apoptosis and cellular activation in the pathogenesis of acute vascular rejection",
abstract = "Acute vascular or humoral rejection, a vexing outcome of organ transplantation, has been attributed by some to activation and by others to apoptosis of endothelial cells in the graft. We asked which of these processes causes acute vascular rejection by tracing the processes during the development of acute vascular rejection in porcine cardiac xenografts performed in baboons. Apoptosis, assayed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), expression of activated caspase-3, and proapoptotic genes Bax and Bcl-xL, was not detected until acute vascular rejection was well advanced, and even then, apoptosis was largely confined to myocytes. Activation of the endothelium, as evidenced by expansion of rough endoplasmic reticulum and increased ribosomal antigen and phospho-p70 S6 kinase, occurred early in the course of acute vascular rejection and progressed through the disease process. These findings suggest that acute vascular rejection is caused by an active metabolic process and not by apoptosis in the endothelium.",
keywords = "Apoptosis, Cardiac transplantation, Endothelial cells, Xenotransplantation",
author = "Holzknecht, {Zoie E.} and Kuypers, {Karisha L.} and Plummer, {Timothy B.} and Josie Williams and Matilda Bustos and Gores, {Gregory James} and Brunn, {Gregory J.} and Platt, {Jeffrey L.}",
year = "2002",
month = "12",
doi = "10.1161/01.RES.0000046236.20251.FA",
language = "English (US)",
volume = "91",
pages = "1135--1141",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "12",

}

TY - JOUR

T1 - Apoptosis and cellular activation in the pathogenesis of acute vascular rejection

AU - Holzknecht, Zoie E.

AU - Kuypers, Karisha L.

AU - Plummer, Timothy B.

AU - Williams, Josie

AU - Bustos, Matilda

AU - Gores, Gregory James

AU - Brunn, Gregory J.

AU - Platt, Jeffrey L.

PY - 2002/12

Y1 - 2002/12

N2 - Acute vascular or humoral rejection, a vexing outcome of organ transplantation, has been attributed by some to activation and by others to apoptosis of endothelial cells in the graft. We asked which of these processes causes acute vascular rejection by tracing the processes during the development of acute vascular rejection in porcine cardiac xenografts performed in baboons. Apoptosis, assayed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), expression of activated caspase-3, and proapoptotic genes Bax and Bcl-xL, was not detected until acute vascular rejection was well advanced, and even then, apoptosis was largely confined to myocytes. Activation of the endothelium, as evidenced by expansion of rough endoplasmic reticulum and increased ribosomal antigen and phospho-p70 S6 kinase, occurred early in the course of acute vascular rejection and progressed through the disease process. These findings suggest that acute vascular rejection is caused by an active metabolic process and not by apoptosis in the endothelium.

AB - Acute vascular or humoral rejection, a vexing outcome of organ transplantation, has been attributed by some to activation and by others to apoptosis of endothelial cells in the graft. We asked which of these processes causes acute vascular rejection by tracing the processes during the development of acute vascular rejection in porcine cardiac xenografts performed in baboons. Apoptosis, assayed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), expression of activated caspase-3, and proapoptotic genes Bax and Bcl-xL, was not detected until acute vascular rejection was well advanced, and even then, apoptosis was largely confined to myocytes. Activation of the endothelium, as evidenced by expansion of rough endoplasmic reticulum and increased ribosomal antigen and phospho-p70 S6 kinase, occurred early in the course of acute vascular rejection and progressed through the disease process. These findings suggest that acute vascular rejection is caused by an active metabolic process and not by apoptosis in the endothelium.

KW - Apoptosis

KW - Cardiac transplantation

KW - Endothelial cells

KW - Xenotransplantation

UR - http://www.scopus.com/inward/record.url?scp=0036950758&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036950758&partnerID=8YFLogxK

U2 - 10.1161/01.RES.0000046236.20251.FA

DO - 10.1161/01.RES.0000046236.20251.FA

M3 - Article

C2 - 12480814

AN - SCOPUS:0036950758

VL - 91

SP - 1135

EP - 1141

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 12

ER -