Genetic engineering of vein grafts resistant to atherosclerosis

Michael J. Mann, Gary H. Gibbons, Robert S. Kernoff, Frank P. Diet, Philip S. Tsao, John P. Cooke, Yasufumi Kaneda, Victor J. Dzau

Research output: Contribution to journalArticle

172 Scopus citations

Abstract

Previously, researchers have speculated that genetic engineering can improve the long-term function of vascular grafts which are prone to atherosclerosis and occlusion. In this study, we demonstrated that an intraoperative gene therapy approach using antisense oligodeoxynucleotide blockage of medial smooth muscle cell proliferation can prevent the accelerated atherosclerosis that is responsible for autologous vein graft failure. Selective blockade of the expression of genes for two cell cycle regulatory proteins, proliferating cell nuclear antigen and cell division cycle 2 kinase, was achieved in the smooth muscle cells of rabbit jugular veins grafted into the carotid arteries. This alteration of gene expression successfully redirected vein graft biology away from neointimal hyperplasia and toward medial hypertrophy, yielding conduits that more closely resembled normal arteries. More importantly, these genetically engineered grafts proved resistant to diet-induced atherosclerosis. These findings establish the feasibility of developing genetically engineered bioprostheses that are resistant to failure and better suited to the long-term treatment of occlusive vascular disease.

Original languageEnglish (US)
Pages (from-to)4502-4506
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number10
DOIs
StatePublished - May 9 1995

Keywords

  • antisense oligodeoxynucleotide
  • gene therapy
  • vascular remodeling
  • vascular surgery

ASJC Scopus subject areas

  • General
  • Genetics

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