2000 ASCB Annual Meeting Press Book - page 8

Beyond Balloons: Blocking
Arteriosclerosis at the
Cellular Level
They use balloons these days to unclog your heart.
Angioplasty, the reopening of obstructed arteries by inflat-
ing a small balloon inside the blocked area, is one of the
great advances of modern cardiology. For most patients, it
leads to immediate relief from the symptoms of arterioscle-
rosis. But for many, the benefits don’t last. More than 40
percent of patients who undergo the procedure will expe-
rience ‘restenosis’ as the open center of the artery
becomes constricted again. Cardiologists have devised bet-
ter techniques and materials, such as ‘stents’ and biocom-
patible metal structures, to support the reopened vessels.
Yet the problem with arteriosclerosis and restenosis is not
mechanical, but biological. The cells in the arterial wall are
stuck in a biological cascade called the inflammatory
response. The ideal treatment would be to coax the cells
themselves into turning off the inflammation. The first
glimmer that such an approach might be possible is now
reported by scientists in Austria.
Arterial inflammation can begin in many ways, such as
a bacterial or viral infection, a cut or wound to the vessel
wall, or a chemical insult such as a lifetime of eating oxi-
dized lipids. Laboratory studies have shown that the
inflammatory response of cells is driven by a transcription
factor named NF-kappa-B. When activated, this factor
enters the cell nucleus and initiates the expression of pro-
teins that cause inflammation. NF-kappa-B is inhibited by a
natural antagonist, a protein named I-kappa-B. Introducing
this natural antagonist into arterial cells might stop the
inflammation, but a method for delivering the antagonist
has eluded researchers.
Though a long way from any human application, a bio-
logical treatment for arteriosclerosis has been shown to be
feasible in rabbits. J.M. Breuss, B.R. Binder, and a team of
Austrian researchers at the University of Vienna used aden-
ovirus to deliver the gene that expresses I-kappa-B into
rabbits. The adenovirus delivered the I-kappa-B gene
directly into the nucleus of the target cells, where the gene
was expressed. These cells responded by producing large
amounts of the inflammation inhibitor, and the treated ani-
mals had a reduced inflammatory response. Although the
use of viruses to deliver genes is still highly experimental
in humans, these results add arteriosclerosis to the list of
diseases that may benefit from future advances in gene
therapy.
40th Annual Meeting
December 9-13, 2000
Moscone Convention Center, San Francisco
3
Contact:
J.M. Breuss
Department of Vascular Biology and Thrombosis
Research
University of Vienna
Telephone: 43-1-4277 625 09, (-42)
Bernd R. Binder
Telephone: 43-1-4277 625 02
Adenoviral gene transfer of I-kappa-B into bal-
looned rabbit iliac arteries prevents negative
remodeling.
Authors:
J. M. Breuss*, M. Cejna**, H. Bergmeister***, A.
Kadl*, G. Baumgartl*, S. Steurer, Z. Xu**, Y.
Koshelnick, R. DeMartin*, U. Losert***, J.
Lammer**, H. Plenk#, B.R. Binder*
*Dept. of Vascular Biology and Thrombosis
Research, University of Vienna, Austria, ** Dept.
of Angiography and Interventional Radiology, ***
Dept. of Biomedical Research, #Dept. of
Histology and Embryology. University of Vienna,
Schwarzspanierstrasse 17, Vienna A-1090, Austria
At The ASCB Meeting
Poster Session Halls A/B/C
P64 - Blood Vessels
Author Presents
Monday, December 11, 1:30 PM-3:00 PM
Program # 1217
Board # B210
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