This report/study is massive, i didnt want to copy and paste the whole thing it goes into results etc etc
Ursolic acid causes DNA-damage, P53-mediated, mitochondria- and
caspase-dependent human endothelial cell apoptosis, and accelerates
atherosclerotic plaque formation in vivo
Barbara Messnera,1, Iris Zeller a,1, Christian Plonerb, Sandra Frotschnigc, Thomas Ringerd,
Anneliese Steinacher-Nigischa, Andreas Ritsche, Günther Laufera, Christian Huckd, David Bernharda,∗
a Cardiac Surgery, Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna, Austria
b Department of Plastic and Reconstructive Surgery, Medical University Innsbruck, Innsbruck, Austria
c Cardiac Surgery Research Laboratory, Department of Cardiac Surgery, Medical University Innsbruck, Innsbruck, Austria
d Institute of Analytical Chemistry and Radiochemistry, Leopold Franzens University Innsbruck, Innsbruck, Austria
e Department of Medicine, Medical University Innsbruck, Innsbruck, Austria
a r t i c l e i n f o
Article history:
Received 24 September 2010
Received in revised form 18 April 2011
Accepted 23 May 2011
Available online xxx
Keywords:
Ursolic acid
Triterpene
Endothelial
Atherosclerosis
Cell death
DNA-damage
P53
BAK
BCLXL
IL-5
Therapy
a b s t r a c t
Objective: The plant derived triterpene ursolic acid (UA) has been intensively studied in the past; mainly
as an anti-cancer compound and for its cardiovascular protective properties. Based on the controversy
of reports suggesting anti-angiogenic and cytotoxic effects of UA on one side and cardiovascular and
endothelial protective effects on the other side, we decided to assess UA effects on primary human
endothelial cells in vitro and atherosclerotic plaque formation in vivo.
Methods and results: Our in vitro analyses clearly show that UA inhibits endothelial proliferation and is
a potent inducer of endothelial cell death. UA causes DNA-damage, followed by the activation of a P53-,
BAK-, and caspase-dependent cell-death pathway. Oral application of UA in APO E knockout mice potently
stimulated atherosclerotic plaque formation in vivo, which was correlated with decreased serum levels
of the athero-protective cytokine IL-5.
Conclusions: Due the potent endothelial cell death inducing activity of UA, a systemic application of UA in
the treatment of cardiovascular diseases seems unfavourable. UA as an anti-angiogenesis, anti-cancer and
– locally applied – cardiovascular drug may be helpful. The DNA damaging activity of UA may however
constitute a serious problem.