title: EGCG attenuates atherosclerosis through the Jagged-1/Notch pathway.
abstract: Atherosclerosis is the most common cause of cardiovascular diseases worldwide. Oxidized low-density lipoprotein (ox-LDL) is a particularly important risk factor in the pathogenesis of atherosclerosis. Accumulating evidence has indicated that epigallocatechin-3-gallate (EGCG; a catechin found in the popular beverage, greent tea) protects against ox-LDL-induced atherosclerosis. However, the underlying mechanisms remain unclear. In the present study, ox-LDL (100 mg/l) induced damage to, and the apoptosis of human umbilical vein endothelial cells (HUVECs) by reducing endothelial nitric oxide synthase (eNOS) expression and promoting inducible nitric oxide synthase (iNOS) expression; these effects were abrogated by the addition of 50 µM EGCG. Furthermore, ox-LDL rapidly activated the membrane translocation of p22phox, and altered the protein expression of Jagged-1 and Notch pathway-related proteins [Math1, hairy and enhancer of split (HES)1 and HES5]; these effects were also prevented by pre-treatment with 50 µM EGCG. In addition, Jagged-1 played a significant role in the EGCG-mediated protection against ox-LDL-induced apoptosis and ox-LDL‑diminished cell adhesion in the HUVECs. Finally, EGCG inhibited high-fat diet (HFD)-induced atherosclerosis in apolipoprotein E (ApoE) knockout (ApoE-KO) mice through the Jagged-1/Notch pathway. Taken together, these findings demonstrate that 50 µM EGCG protects against ox-LDL-induced endothelial dysfunction through the Jagged-1/Notch signaling pathway. Moreover, our data provide insight into the possible molecular mechanisms through which EGCG attenuates ox-LDL‑induced vascular endothelial dysfunction.
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Cardiology, The First Hospital of Changsha, Changsha, Hunan 410011, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Yi
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Daoquan
authors.initials: D
authors.lastname: Peng
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015971:Gene Expression Regulation, Enzymologic; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D000072100:Jagged-1 Protein; D008077:Lipoproteins, LDL / Q000633:toxicity; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D051880:Receptors, Notch / Q000096:biosynthesis* / Q000235:genetics; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001057:Apolipoproteins E; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; C099252:oxidized low density lipoprotein; D002392:Catechin; C045651:epigallocatechin gallate; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III