New therapeutic possibilities for vein graft disease in the post-edifoligide era.


Journal Article

Vein graft neointimal hyperplasia involves proliferation and migration of vascular smooth muscle cells into the vessel intima, and ultimately engenders accelerated atherosclerosis and vein graft failure. Since a myriad of stimuli provoke smooth muscle cell proliferation, molecular therapies for vein graft disease have targeted mechanisms fundamental to all cell proliferation - the 'cell-cycle' machinery. Preclinically, the most successful of these therapies has been edifoligide (E2F decoy), a double-stranded oligodeoxynucleotide that binds to the transcription factor known as E2F. Recently, PRoject of Ex vivo vein GRaft Engineering via Transfection (PREVENT) III and IV demonstrated that edifoligide failed to benefit human vein grafts employed to treat lower-extremity ischemia and coronary heart disease, respectively. The clinical failure of edifoligide calls into question previous models of vein graft disease and lends credence to recent animal studies demonstrating that vein graft arterialization substantially involves the immigration into the vein graft of a variety of vascular progenitor cells. Future vein graft disease therapies will likely target not only proliferation of graft-intrinsic cells, but also immigration of graft-extrinsic cells.

Full Text

Duke Authors

Cited Authors

  • Cai, X; Freedman, NJ

Published Date

  • July 2006

Published In

Volume / Issue

  • 2 / 4

Start / End Page

  • 493 - 501

PubMed ID

  • 19804184

Pubmed Central ID

  • 19804184

Electronic International Standard Serial Number (EISSN)

  • 1744-8298

Digital Object Identifier (DOI)

  • 10.2217/14796678.2.4.493


  • eng

Conference Location

  • England