Nature Medicine
4, 222 - 227 (1998)
doi:10.1038/nm0298-222
Inhibition of neointimal cell bcl-x expression induces apoptosis and regression of vascular diseaseMatthew J. Pollman1, Jennifer L. Hall2, Michael J. Mann2, Lunan Zhang2
& Gary H. Gibbons2, 3
1Falk Cardiovascular Research Center, Division of Cardiovascular Medicine, Stanford University, 300 Pasteur Drive, Stanford, California 94305-5246, USA
2Brigham and Women's Hospital, Thorn Cardiovascular Research Laboratories, 1326, 75 Francis Street, Boston, Massachusetts 02115, USA
3e-mail: ggibbons@bustoff.bwh.harvard.edu 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-x
L 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-x
L are critical determinants of intimal lesion formation and that targeted apoptosis may be a novel therapy for intimal vascular disease.
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