Dietary quercetin attenuates oxidant-induced endothelial dysfunction and atherosclerosis in apolipoprotein E knockout mice fed a high-fat diet: A critical role for heme oxygenase-1

作者：Shen Yu; Ward Natalie C; Hodgson Jonathan M; Puddey Ian B; Wang Yutang; Zhang Di; Maghzal Ghassan J; Stocker Roland; Croft Kevin D^*

来源：Free Radical Biology and Medicine, 2013, 65: 908-915.

DOI：10.1016/j.freeradbiomed.2013.08.185

• Polyphenol
• Flavonoid
• Quercetin
• Endothelial function
• Atherosclerosis
• HO-1
• NO
• Oxidative stress

Several lines of evidence indicate that quercetin, a polyphenol derived in the diet from fruit and vegetables, contributes to cardiovascular health. We aimed to investigate the effects of dietary quercetin on endothelial function and atherosclerosis in mice fed a high-fat diet. Wild-type C57BL/6 (WT) and apolipoprotein E gene knockout (ApoE(-/-)) mice were fed: (i) a high-fat diet (HFD) or (ii) a HFD supplemented with 0.05% w/w quercetin (HFD + Q), for 14 weeks. Compared with animals fed HFD, HFD+Q attenuated atherosclerosis in ApoE-/- mice. Treatment with the HFD+Q significantly improved endothelium-dependent relaxation of aortic rings isolated from WT but not ApoE-/- mice and attenuated hypochlorous acid-induced endothelial dysfunction in aortic rings of both WT and ApoE(-/-) mice. Mechanistic studies revealed that HFD + Q significantly improved plasma F-2-isoprostanes, 24 h urinary nitrite, and endothelial nitric oxide synthase activity, and increased heme oxygenase-1 (HO-1) protein expression in the aortas of both WT and ApoE-/- mice (P%26lt;0.05). HFD+Q also resulted in small changes in plasma cholesterol (P%26lt;0.05 in WT) and plasma triacylglycerols (P%26lt;0.05 in ApoE(-/-) mice). In a separate experiment, quercetin did not protect against hypochlorite-induced endothelial dysfunction in arteries obtained from heterozygous HO-1 gene knockout mice with low expression of HO-1 protein. Quercetin protects mice fed a HFD against oxidant-induced endothelial dysfunction and ApoE-/- mice against atherosclerosis. These effects are associated with improvements in nitric oxide bioavailability and are critically related to arterial induction of HO-1.

• 出版日期2013-12
• 单位南京大学