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Inhibition of neointimal cell bcl-x expression induces apoptosis and regression of vascular disease

Nature Medicinevolume 4pages222227 (1998) | Download Citation

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Abstract

We postulated that activation of a genetic program that tonicaiiy inhibits intimal cell death is a necessary condition for the pathogenesis of vascular disease. Studies of vascular lesions in humans and animal models documented increased expression of the anti-apoptotic gene product Bcl-xL within intimal cells. Downregulation of intimal cell bcl-xL expression with the use of antisense oligonucleotides induced apoptosis and acute regression of vascular lesions. These findings indicate that apoptosis regulatory genes such as bcl-xL are critical determinants of intimal lesion formation and that targeted apoptosis may be a novel therapy for intimal vascular disease.

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Affiliations

  1. Falk Cardiovascular Research Center, Division of Cardiovascular Medicine, Stanford University, 300 Pasteur Drive, Stanford, California, 94305-5246, USA

    • Matthew J. Pollman
  2. Brigham and Women's Hospital, Thorn Cardiovascular Research Laboratories, 1326, 75 Francis Street, Boston, Massachusetts, 02115, USA

    • Jennifer L. Hall
    • , Michael J. Mann
    • , Lunan Zhang
    •  & Gary H. Gibbons

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Correspondence to Gary H. Gibbons.

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https://doi.org/10.1038/nm0298-222

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