Low-dose phloretin alleviates diabetic atherosclerosis through endothelial KLF2 restoration

作者：Yong Xia, Hua Feng, Zhenwei Li, Kuanxiao Tang, Haiqing Gao, Weiling Wang, Xiaopei Cui, Xiaoli Li · 发表于：Bioscience Biotechnology and Biochemistry · 年份：2019 · DOI：10.1080/09168451.2019.1699396 · 被引用次数：20 · 研究领域：Kruppel-like factors research、Peroxisome Proliferator-Activated Receptors、Metabolism, Diabetes, and Cancer

ABSTRACT We investigated whether low-dose phloretin served as daily dietary supplements could ameliorate diabetic atherosclerosis and the role of kruppel-like factor 2 (KLF2). HUVECs cultured in high glucose medium were treated with different concentrations of phloretin and KLF2 mRNA, and protein level was detected. Diabetes was induced using streptozotocin in Apoe−/- mice after which they were fed a high-cholesterol diet for 8 weeks. Diabetic mice injected with KLF2 shRNA-lentivirus or control virus were treated with 20 mg/kg phloretin. Glucose, lipid profile, aortic atheroma, and endothelial nitric oxide synthase (eNOS) expression were detected. Phloretin retained endothelial function by KLF2-eNOS activation under hyperglycemia. Low-dose phloretin helped with lipid metabolism, and blocked the acceleration of atherosclerosis in STZ-induced diabetic mice since the early stage, which was diminished by KLF2 knockdown. Low-dose phloretin exhibited athero-protective effect in diabetic Apoe−/- mice dependent on KLF2 activation. This finding makes phloretin for diabetic atherosclerosis.