Resveratrol protects against atherosclerosis, but does not add to the antiatherogenic effect of atorvastatin, in APOE*3-Leiden.CETP mice.
Resveratrol is a major constituent of traditional Asian medicinal herbs and red wine and is suggested to be a potential antiatherosclerotic drug due to its proposed hypolipidemic, anti-inflammatory and antioxidative properties. The aim of this study was to evaluate whether resveratrol protects against atherosclerosis development in APOE*3-Leiden.CETP (E3L.CETP) mice and adds to the antiatherogenic effect of mild statin treatment, currently the most widely used antiatherogenic therapy. E3L.CETP mice were fed a cholesterol-rich diet without (control) or with resveratrol (0.01% w/w), atorvastatin (0.0027% w/w) or both for 14 weeks. During the study plasma lipid, inflammatory and oxidative stress parameters were determined. Resveratrol reduced atherosclerotic lesion area (-52%) in the aortic root, comparable to atorvastatin (-40%) and the combination of both drugs (-47%). The collagen/macrophage ratio in the atherosclerotic lesion, a marker of plaque stability, was increased by resveratrol (+108%), atorvastatin (+124%) and the combination (+154%). Resveratrol decreased plasma cholesterol levels (-19%) comparable to atorvastatin (-19%) and the combination (-22%), which was completely confined to (very)low-density lipoprotein cholesterol levels in all groups. Post hoc analyses showed that the antiatherogenic effect of atorvastatin could be explained by cholesterol lowering, while the antiatherosclerotic effect of resveratrol could be attributed to factors additional to cholesterol lowering. Markers of inflammation and oxidative stress were not different, but resveratrol improved macrophage function. We conclude that resveratrol potently reduces atherosclerosis development and induces a more stable lesion phenotype in E3L.CETP mice. However, under the experimental conditions tested, resveratrol does not add to the antiatherogenic effect of atorvastatin.
['Berbée|Jimmy F P|JF|', 'Wong|Man C|MC|', 'Wang|Yanan|Y|', 'van der Hoorn|José W A|JW|', 'Khedoe|Padmini P S J|PP|', 'van Klinken|Jan B|JB|', 'Mol|Isabel M|IM|', 'Hiemstra|Pieter S|PS|', 'Tsikas|Dimitrios|D|', 'Romijn|Johannes A|JA|', 'Havekes|Louis M|LM|', 'Princen|Hans M G|HM|', 'Rensen|Patrick C N|PC|']
D000818:Animals D050197:Atherosclerosis D000069059:Atorvastatin D015415:Biomarkers D002791:Cholesterol, Dietary D008078:Cholesterol, LDL D004357:Drug Synergism D005260:Female D006538:Heptanoic Acids D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors D007249:Inflammation D051379:Mice D008822:Mice, Transgenic D018384:Oxidative Stress D011758:Pyrroles D000077185:Resveratrol D013267:Stilbenes
Resveratrol Atherosclerosis CETP Statin Lipids Oxidative stress Inflammation 3-hydroxy-3-methylglutaryl coenzyme A reductase 8-iso-PGF(2α) APOE*3-Leiden transgenic CXCL1 E3L HMG-CoA reductase IL Ig LPS MCP-1 RT-PCR SMC TG WTD Western-type diet chemokine (C-X-C motif) ligand-1 cholesteryl ester transfer protein cox1/-2, cyclooxygenase-1/-2 immunoglobulin interleukin isoprostane 15(S)-8-iso-prostaglandin F(2α) lectin-like oxidized low-density lipoprotein receptor-1 lipopolysaccharide lox-1 manganese superoxide dismutase mnsod monocyte chemoattractant protein-1 oxLDL oxidized LDL paraoxonase-1 pon1 real-time polymerase chain reaction sE-selectin smooth muscle cell soluble E-selectin triglycerides