Recombinant mitotoxin basic fibroblast growth factor-saporin reduces venous anastomotic intimal hyperplasia in the arteriovenous graft

Changyi Chen, Samer Mattar, John D. Hughes, Glenn F. Pierce, Jennifer E. Cook, David N. Ku, Stephen R. Hanson, Alan B. Lumsden

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: The plant cytotoxin saporin (SAP) is a potent ribosome- inactivating protein. When conjugated to basic fibroblast growth factor (FGF2), it selectively kills proliferating cells that have upregulated FGF receptors. In this study, we evaluated the effect of the recombinant chimeric mitotoxin rFGF2-SAP on venous anastomotic intimal hyperplasia, a major cause of failure of arteriovenous (AV) grafts. Methods and Results: Recently designed expanded polytetrafluoroethylene-based local infusion devices were implanted bilaterally as femoral AV conduits in six dogs. The venous anastomoses were the sites of continuous delivery of rFGF2-SAP (2.7 μg · kg-1 · d-1) to one side and vehicle (4.6 μL · kg-1 · d-1) as control to the contralateral side for 14 days. All animals survived, and all grafts were patent. Liver enzyme levels and histological analyses of liver, kidneys, and brain were normal, indicating the absence of systemic toxicity. Morphometric measurements and measurements of cell proliferation by bromodeoxyuridine index analysis were performed at both arterial and venous anastomoses. There were no significant differences between the treated grafts and the control grafts in intimal hyperplasia and intimal cell proliferation at the arterial anastomoses. In contrast, rFGF2-SAP reduced intimal thickness by 32%, intimal area by 40%, and cell proliferation index by 33% at the treated venous anastomoses compared with the control venous anastomoses (P

Original languageEnglish (US)
Pages (from-to)1989-1995
Number of pages7
JournalCirculation
Volume94
Issue number8
StatePublished - 1996
Externally publishedYes

Fingerprint

Tunica Intima
Hyperplasia
Transplants
Cell Proliferation
Fibroblast Growth Factor 2
Ribosome Inactivating Proteins
Fibroblast Growth Factor Receptors
Liver
Cytotoxins
Polytetrafluoroethylene
Bromodeoxyuridine
Thigh
recombinant basic fibroblast growth factor-saporin mitotoxin
Dogs
Kidney
Equipment and Supplies
saporin
Brain
Enzymes

Keywords

  • grafting
  • growth substances
  • hyperplasia
  • saporin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Chen, C., Mattar, S., Hughes, J. D., Pierce, G. F., Cook, J. E., Ku, D. N., ... Lumsden, A. B. (1996). Recombinant mitotoxin basic fibroblast growth factor-saporin reduces venous anastomotic intimal hyperplasia in the arteriovenous graft. Circulation, 94(8), 1989-1995.

Recombinant mitotoxin basic fibroblast growth factor-saporin reduces venous anastomotic intimal hyperplasia in the arteriovenous graft. / Chen, Changyi; Mattar, Samer; Hughes, John D.; Pierce, Glenn F.; Cook, Jennifer E.; Ku, David N.; Hanson, Stephen R.; Lumsden, Alan B.

In: Circulation, Vol. 94, No. 8, 1996, p. 1989-1995.

Research output: Contribution to journalArticle

Chen, C, Mattar, S, Hughes, JD, Pierce, GF, Cook, JE, Ku, DN, Hanson, SR & Lumsden, AB 1996, 'Recombinant mitotoxin basic fibroblast growth factor-saporin reduces venous anastomotic intimal hyperplasia in the arteriovenous graft', Circulation, vol. 94, no. 8, pp. 1989-1995.
Chen, Changyi ; Mattar, Samer ; Hughes, John D. ; Pierce, Glenn F. ; Cook, Jennifer E. ; Ku, David N. ; Hanson, Stephen R. ; Lumsden, Alan B. / Recombinant mitotoxin basic fibroblast growth factor-saporin reduces venous anastomotic intimal hyperplasia in the arteriovenous graft. In: Circulation. 1996 ; Vol. 94, No. 8. pp. 1989-1995.
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AU - Lumsden, Alan B.

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