PMID- 22535762 OWN - NLM STAT- MEDLINE DCOM- 20120725 LR - 20230216 IS - 1541-6100 (Electronic) IS - 0022-3166 (Linking) VI - 142 IP - 6 DP - 2012 Jun TI - Supplementation with cyanidin-3-O-beta-glucoside protects against hypercholesterolemia-mediated endothelial dysfunction and attenuates atherosclerosis in apolipoprotein E-deficient mice. PG - 1033-7 LID - 10.3945/jn.112.157701 [doi] AB - In this study, we investigated the protective effects of the anthocyanin cyanidin-3-O-beta-glucoside (C3G) on hypercholesterolemia-induced endothelial dysfunction in apoE-deficient (apoE(-/-)) mice. In the prevention study, twenty 8-wk-old male apoE(-/-) mice (n = 10/group) were fed a high-fat, cholesterol-rich diet (HCD) or the HCD supplemented with C3G (2 g/kg diet) for 8 wk. The endothelium-dependent relaxation response to acetylcholine in the aortas of the C3G-fed mice was greater compared with those fed the HCD (P < 0.05). The atherosclerotic plaque area in the aortic sinus of mice fed the C3G diet was lowered by 54% compared with those fed the HCD (P < 0.01). Mice fed C3G had greater expression of the ATP-binding cassette transporter G1 (ABCG1) and lower cholesterol, mainly 7-ketocholesterol (7-KC), concentrations than those fed the HCD. Superoxide production and lipid hydroperoxides in aorta were lower in mice fed C3G compared with those fed the HCD. The phosphorylation levels at Ser1177 of endothelial NO synthase (eNOS) and the production of cyclic GMP (cGMP) in aorta were greater in C3G-fed mice than in HCD-fed mice. In the therapy study, apoE(-/-) mice were fed the HCD for 8 wk and then continued to receive the HCD or were switched to the HCD supplemented with C3G (2 g/kg diet) for another 8 wk. The established endothelial dysfunction and atherosclerosis were reversed, accompanied by greater ABCG1 expression in aorta, lower cholesterol and 7-KC concentrations, and greater generation of cGMP in mice fed C3G compared with those fed the HCD. Taken together, our results show that the anthocyanin C3G prevents or reverses hypercholesterolemia-induced endothelial dysfunction by inhibiting cholesterol and 7-oxysterol accumulation in the aorta and the subsequent decrease in superoxide production, thereby preserving eNOS activity and NO bioavailability. FAU - Wang, Yun AU - Wang Y AD - Department of Nutrition, Sun Yat-sen University, Guangzhou, Guangdong Province, People's Republic of China FAU - Zhang, Yuhua AU - Zhang Y FAU - Wang, Xiaoming AU - Wang X FAU - Liu, Yan AU - Liu Y FAU - Xia, Min AU - Xia M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120425 PL - United States TA - J Nutr JT - The Journal of nutrition JID - 0404243 RN - 0 (Anthocyanins) RN - 0 (Apolipoproteins E) RN - 0 (Dietary Fats) RN - 0 (Glucosides) RN - 0 (Hypolipidemic Agents) RN - 0 (cyanidin-3-O-beta-glucopyranoside) RN - 31C4KY9ESH (Nitric Oxide) SB - IM MH - Animals MH - Anthocyanins/*pharmacology MH - Aorta/drug effects/pathology MH - Apolipoproteins E/genetics/*metabolism MH - Atherosclerosis/genetics/*prevention & control MH - Dietary Fats/administration & dosage/adverse effects MH - Dietary Supplements MH - Endothelium, Vascular/drug effects/physiopathology MH - Glucosides/*pharmacology MH - Hypercholesterolemia/drug therapy/*physiopathology MH - Hypolipidemic Agents/*pharmacology MH - Male MH - Mice MH - Mice, Knockout MH - Nitric Oxide MH - Oxidative Stress EDAT- 2012/04/27 06:00 MHDA- 2012/07/26 06:00 CRDT- 2012/04/27 06:00 PHST- 2012/04/27 06:00 [entrez] PHST- 2012/04/27 06:00 [pubmed] PHST- 2012/07/26 06:00 [medline] AID - S0022-3166(22)02792-4 [pii] AID - 10.3945/jn.112.157701 [doi] PST - ppublish SO - J Nutr. 2012 Jun;142(6):1033-7. doi: 10.3945/jn.112.157701. Epub 2012 Apr 25.