Fibrin matrix for local delivery of a mitotoxin to inhibit vascular smooth muscle cell proliferation

T. E. Brothers, J. Boggs, C. Goldsmith, A. E. Frankel, M. C. Willingham

Research output: Contribution to journalArticle

Abstract

Successful use of mitotoxins to inhibit neointimal hyperplasia after vascular graft implantation will require local delivery of high concentrations of the toxin. As a first step to determine the feasibility of using a fibrin matrix delivery system for prosthetic grafts, we studied the effect of fibrin incorporation on the toxicity of a mitotoxin directed against the epidermal growth factor receptor on porcine vascular cells. Inhibition of protein synthesis as determined by 3H-leucine uptake was greater in smooth muscle cells (ICso 50 pM) compared with endothelial cells (ICso 5.0 nM). Fibrin clot incorporation of the 48 kd mitotoxin, accomplished by the addition of 0.32 U/ml thrombin and 32 mg/ml fibrinogen, prevented all inhibitory activity. Toxicity could be partially restored (ICso 70 nM) by coincubation of the mitotoxm-fibrin matrix with 250 U/ml urokinase. Using this fibrin matrix delivery system, therapeutic levels of this mitotoxin cannot be attained by diffusion alone, but will require local fibrinolvsis.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - 1996

Fingerprint

fibrin
Cell proliferation
Fibrin
Vascular Smooth Muscle
blood vessels
smooth muscle
myocytes
Smooth Muscle Myocytes
Muscle
cell proliferation
Cell Proliferation
Grafts
Blood Vessels
Toxicity
toxicity
u-plasminogen activator
Transplants
thrombin
Endothelial cells
Urokinase-Type Plasminogen Activator

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Fibrin matrix for local delivery of a mitotoxin to inhibit vascular smooth muscle cell proliferation. / Brothers, T. E.; Boggs, J.; Goldsmith, C.; Frankel, A. E.; Willingham, M. C.

In: FASEB Journal, Vol. 10, No. 3, 1996.

Research output: Contribution to journalArticle

Brothers, T. E. ; Boggs, J. ; Goldsmith, C. ; Frankel, A. E. ; Willingham, M. C. / Fibrin matrix for local delivery of a mitotoxin to inhibit vascular smooth muscle cell proliferation. In: FASEB Journal. 1996 ; Vol. 10, No. 3.
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AU - Willingham, M. C.

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