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Decreased fibrinolytic activity in porcine-to-primate cardiac xenotransplantation.

Publication ,  Journal Article
Kalady, MF; Lawson, JH; Sorrell, RD; Platt, JL
Published in: Mol Med
September 1998

BACKGROUND: One major barrier to successful xenotransplantation is acute vascular rejection, a process pathologically characterized by microvascular thrombosis and diffuse fibrin deposition in transplant blood vessels. This pathologic picture may result from a disturbance in the coagulant or fibrinolytic pathways that regulate normal vascular patency. This study evaluated the regulation of fibrinolytic activity defined by tissue plasminogen activator and plasminogen activator inhibitor-1 as it may exist in the setting of acute vascular rejection. MATERIALS AND METHODS, RESULTS: Serial biopsies from cardiac xenotransplants evaluated by immunofluorescence microscopy demonstrated progressive decreases in tissue plasminogen activator and increases in plasminogen activator inhibitor-1. In vitro studies measuring fibrinolytic activity of cell culture medium from porcine aortic endothelial cells stimulated with human serum or autologous porcine serum revealed that human serum triggered as much as 93% increase in antifibrinolytic activity. CONCLUSIONS: These findings demonstrate that porcine vascular endothelial cells change toward an antifibrinolytic state following stimulation with human xenoreactive antibodies and complement. The shift is at least partly explained by an increased ratio of plasminogen activator inhibitor-1 to tissue plasminogen activator, and is at least in part mediated by the activation of complement. This increased antifibrinolytic activity may contribute to the thrombotic diathesis seen in acute vascular rejection in pig-to-primate xenografts.

Duke Scholars

Published In

Mol Med

ISSN

1076-1551

Publication Date

September 1998

Volume

4

Issue

9

Start / End Page

629 / 637

Location

England

Related Subject Headings

  • Transplantation, Heterologous
  • Tissue Plasminogen Activator
  • Swine
  • Plasminogen Activator Inhibitor 1
  • Papio
  • Kinetics
  • Immunology
  • Humans
  • Homeostasis
  • Heart Transplantation
 

Citation

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Kalady, M. F., Lawson, J. H., Sorrell, R. D., & Platt, J. L. (1998). Decreased fibrinolytic activity in porcine-to-primate cardiac xenotransplantation. Mol Med, 4(9), 629–637.
Kalady, M. F., J. H. Lawson, R. D. Sorrell, and J. L. Platt. “Decreased fibrinolytic activity in porcine-to-primate cardiac xenotransplantation.Mol Med 4, no. 9 (September 1998): 629–37.
Kalady MF, Lawson JH, Sorrell RD, Platt JL. Decreased fibrinolytic activity in porcine-to-primate cardiac xenotransplantation. Mol Med. 1998 Sep;4(9):629–37.
Kalady, M. F., et al. “Decreased fibrinolytic activity in porcine-to-primate cardiac xenotransplantation.Mol Med, vol. 4, no. 9, Sept. 1998, pp. 629–37.
Kalady MF, Lawson JH, Sorrell RD, Platt JL. Decreased fibrinolytic activity in porcine-to-primate cardiac xenotransplantation. Mol Med. 1998 Sep;4(9):629–637.

Published In

Mol Med

ISSN

1076-1551

Publication Date

September 1998

Volume

4

Issue

9

Start / End Page

629 / 637

Location

England

Related Subject Headings

  • Transplantation, Heterologous
  • Tissue Plasminogen Activator
  • Swine
  • Plasminogen Activator Inhibitor 1
  • Papio
  • Kinetics
  • Immunology
  • Humans
  • Homeostasis
  • Heart Transplantation