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Cell cycle inhibition preserves endothelial function in genetically engineered rabbit vein grafts.

Publication ,  Journal Article
Mann, MJ; Gibbons, GH; Tsao, PS; von der Leyen, HE; Cooke, JP; Buitrago, R; Kernoff, R; Dzau, VJ
Published in: J Clin Invest
March 15, 1997

We have recently shown that ex vivo gene therapy of rabbit autologous vein grafts with antisense oligodeoxynucleotides (AS ODN) blocking cell cycle regulatory gene expression inhibits not only neointimal hyperplasia, but also diet-induced, accelerated graft atherosclerosis. We observed that these grafts remained free of macrophage invasion and foam cell deposition. Since endothelial dysfunction plays an important role in vascular disease, the current study examined the effect of this genetic engineering strategy on graft endothelial function and its potential relationship to the engineered vessels' resistance to atherosclerosis. Rabbit vein grafts transfected with AS ODN against proliferating cell nuclear antigen (PCNA) and cell division cycle 2 (cdc2) kinase elaborated significantly more nitric oxide and exhibited greater vasorelaxation to both calcium ionophore and acetylcholine than did untreated or control ODN-treated grafts. This preservation of endothelial function was associated with a reduction in superoxide radical generation, vascular cell adhesion molecule-1 (VCAM-1) expression, and monocyte binding activity in grafts in both normal and hypercholesterolemic rabbits. Our data demonstrate that AS ODN arrest of vascular cell cycle progression results in the preservation of normal endothelial phenotype and function, thereby influencing the biology of the vessel wall towards a reduction of its susceptibility to occlusive disease.

Duke Scholars

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

March 15, 1997

Volume

99

Issue

6

Start / End Page

1295 / 1301

Location

United States

Related Subject Headings

  • Transfection
  • Thionucleotides
  • Superoxides
  • Rabbits
  • Proliferating Cell Nuclear Antigen
  • Oligonucleotides, Antisense
  • Monocytes
  • Jugular Veins
  • Immunology
  • Growth Inhibitors
 

Citation

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Mann, M. J., Gibbons, G. H., Tsao, P. S., von der Leyen, H. E., Cooke, J. P., Buitrago, R., … Dzau, V. J. (1997). Cell cycle inhibition preserves endothelial function in genetically engineered rabbit vein grafts. J Clin Invest, 99(6), 1295–1301. https://doi.org/10.1172/JCI119288
Mann, M. J., G. H. Gibbons, P. S. Tsao, H. E. von der Leyen, J. P. Cooke, R. Buitrago, R. Kernoff, and V. J. Dzau. “Cell cycle inhibition preserves endothelial function in genetically engineered rabbit vein grafts.J Clin Invest 99, no. 6 (March 15, 1997): 1295–1301. https://doi.org/10.1172/JCI119288.
Mann MJ, Gibbons GH, Tsao PS, von der Leyen HE, Cooke JP, Buitrago R, et al. Cell cycle inhibition preserves endothelial function in genetically engineered rabbit vein grafts. J Clin Invest. 1997 Mar 15;99(6):1295–301.
Mann, M. J., et al. “Cell cycle inhibition preserves endothelial function in genetically engineered rabbit vein grafts.J Clin Invest, vol. 99, no. 6, Mar. 1997, pp. 1295–301. Pubmed, doi:10.1172/JCI119288.
Mann MJ, Gibbons GH, Tsao PS, von der Leyen HE, Cooke JP, Buitrago R, Kernoff R, Dzau VJ. Cell cycle inhibition preserves endothelial function in genetically engineered rabbit vein grafts. J Clin Invest. 1997 Mar 15;99(6):1295–1301.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

March 15, 1997

Volume

99

Issue

6

Start / End Page

1295 / 1301

Location

United States

Related Subject Headings

  • Transfection
  • Thionucleotides
  • Superoxides
  • Rabbits
  • Proliferating Cell Nuclear Antigen
  • Oligonucleotides, Antisense
  • Monocytes
  • Jugular Veins
  • Immunology
  • Growth Inhibitors