Differential effects of green tea-derived catechin on developing versus established atherosclerosis in apolipoprotein E-null mice.
BACKGROUND
Oxidative stress has been implicated in vascular injury and atherogenesis, and antioxidant treatment has shown favorable results in preclinical studies. Despite this, antioxidant therapy has failed to show benefit in clinical trials. Failure of antioxidants in clinical trials may be partly because such therapy is started after atherosclerosis is already well established, whereas the benefits in animal models may be results from early initiation of antioxidants while atherosclerosis is still evolving.


RESULTS
To test this hypothesis, we evaluated the effect of epigallocatechin gallate (EGCG), the main antioxidant derived from green tea, on evolving and established atherosclerotic lesions in hypercholesterolemic apolipoprotein E-null mice. Established native aortic atherosclerotic lesions and evolving atherosclerotic lesions produced by periadventitial cuff injury to carotid arteries were assessed in mice after 21 and 42 days of treatment with daily intraperitoneal injections of EGCG (10 mg/kg) or PBS. EGCG treatment resulted in an increase in the antioxidant capacity in local vascular tissue and systemic circulation and reduced vascular smooth muscle cell proliferation and redox-sensitive gene activation in vitro. EGCG reduced cuff-induced evolving atherosclerotic plaque size at 21 and 42 days by 55% and 73%, respectively, compared with PBS treatment (P<0.05). Conversely, EGCG had no effect on established lesions in the aortic sinuses or the rest of the aorta.


CONCLUSIONS
Our data suggest that antioxidant EGCG differentially reduces evolving atherosclerotic lesions without influencing established atherosclerosis in the apolipoprotein E-null mice.
Chyu
Kuang-Yuh
KY
Atherosclerosis Research Center, Division of Cardiology, and Department of Medicine, Cedars-Sinai Medical Center and David Geffen School of Medicine at the University of California, Los Angeles, CA 90048, USA. chyuk@cshs.org
Babbidge
Stephanie M
SM
Zhao
Xiaoning
X
Dandillaya
Ram
R
Rietveld
Anton G
AG
Yano
Juliana
J
Dimayuga
Paul
P
Cercek
Bojan
B
Shah
Prediman K
PK
D000818:Animals; D000975:Antioxidants / Q000032:analysis / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000235:genetics*; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D028241:Camellia sinensis / Q000737:chemistry; D002340:Carotid Artery Diseases / Q000188:drug therapy / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use*; D002455:Cell Division; D002784:Cholesterol / Q000097:blood; D018450:Disease Progression; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018808:Transcription Factor AP-1 / Q000378:metabolism
D000975:Antioxidants; D001057:Apolipoproteins E; D018808:Transcription Factor AP-1; D002392:Catechin; D002784:Cholesterol; C045651:epigallocatechin gallate; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse