Differential effects of green tea-derived catechin on developing versus established atherosclerosis in apolipoprotein E-null mice

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 s...

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Veröffentlicht in:Circulation (New York, N.Y.) N.Y.), 2004-05, Vol.109 (20), p.2448-2453
Hauptverfasser: CHYU, Kuang-Yuh, BABBIDGE, Stephanie M, XIAONING ZHAO, DANDILLAYA, Ram, RIETVELD, Anton G, YANO, Juliana, DIMAYUGA, Paul, CERCEK, Bojan, SHAH, Prediman K
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container_issue 20
container_start_page 2448
container_title Circulation (New York, N.Y.)
container_volume 109
creator CHYU, Kuang-Yuh
BABBIDGE, Stephanie M
XIAONING ZHAO
DANDILLAYA, Ram
RIETVELD, Anton G
YANO, Juliana
DIMAYUGA, Paul
CERCEK, Bojan
SHAH, Prediman K
description 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. 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
doi_str_mv 10.1161/01.cir.0000128034.70732.c2
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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. 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&lt;0.05). Conversely, EGCG had no effect on established lesions in the aortic sinuses or the rest of the aorta. 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Vascular system ; Cardiovascular system ; Carotid Artery Diseases - drug therapy ; Carotid Artery Diseases - pathology ; Catechin - analogs &amp; derivatives ; Catechin - blood ; Catechin - therapeutic use ; Cell Division ; Cholesterol - blood ; Disease Progression ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Male ; Medical sciences ; Mice ; Mice, Knockout ; Muscle, Smooth, Vascular - cytology ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - pathology ; Nitric Oxide Synthase - metabolism ; Nitric Oxide Synthase Type II ; Pharmacology. Drug treatments ; Transcription Factor AP-1 - metabolism ; Vasodilator agents. 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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. 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&lt;0.05). Conversely, EGCG had no effect on established lesions in the aortic sinuses or the rest of the aorta. Our data suggest that antioxidant EGCG differentially reduces evolving atherosclerotic lesions without influencing established atherosclerosis in the apolipoprotein E-null mice.</description><subject>Animals</subject><subject>Antioxidants - analysis</subject><subject>Antioxidants - therapeutic use</subject><subject>Apolipoproteins E - genetics</subject><subject>Arteriosclerosis - drug therapy</subject><subject>Arteriosclerosis - metabolism</subject><subject>Arteriosclerosis - pathology</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Camellia sinensis - chemistry</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular system</subject><subject>Carotid Artery Diseases - drug therapy</subject><subject>Carotid Artery Diseases - pathology</subject><subject>Catechin - analogs &amp; derivatives</subject><subject>Catechin - blood</subject><subject>Catechin - therapeutic use</subject><subject>Cell Division</subject><subject>Cholesterol - blood</subject><subject>Disease Progression</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Muscle, Smooth, Vascular - cytology</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Muscle, Smooth, Vascular - pathology</subject><subject>Nitric Oxide Synthase - metabolism</subject><subject>Nitric Oxide Synthase Type II</subject><subject>Pharmacology. Drug treatments</subject><subject>Transcription Factor AP-1 - metabolism</subject><subject>Vasodilator agents. 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ispartof Circulation (New York, N.Y.), 2004-05, Vol.109 (20), p.2448-2453
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source MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Ovid Autoload
subjects Animals
Antioxidants - analysis
Antioxidants - therapeutic use
Apolipoproteins E - genetics
Arteriosclerosis - drug therapy
Arteriosclerosis - metabolism
Arteriosclerosis - pathology
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Blood and lymphatic vessels
Camellia sinensis - chemistry
Cardiology. Vascular system
Cardiovascular system
Carotid Artery Diseases - drug therapy
Carotid Artery Diseases - pathology
Catechin - analogs & derivatives
Catechin - blood
Catechin - therapeutic use
Cell Division
Cholesterol - blood
Disease Progression
Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous
Male
Medical sciences
Mice
Mice, Knockout
Muscle, Smooth, Vascular - cytology
Muscle, Smooth, Vascular - drug effects
Muscle, Smooth, Vascular - pathology
Nitric Oxide Synthase - metabolism
Nitric Oxide Synthase Type II
Pharmacology. Drug treatments
Transcription Factor AP-1 - metabolism
Vasodilator agents. Cerebral vasodilators
title Differential effects of green tea-derived catechin on developing versus established atherosclerosis in apolipoprotein E-null mice
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