EGCG attenuates atherosclerosis through the Jagged-1/Notch pathway

Yin,Jianguo; Huang,Fang; Yi,Yuhong; Yin,Liang; Peng,Daoquan

doi:10.3892/ijmm.2015.2422

EGCG attenuates atherosclerosis through the Jagged-1/Notch pathway

Authors:
- Jianguo Yin
- Fang Huang
- Yuhong Yi
- Liang Yin
- Daoquan Peng
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Affiliations: Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China, Department of Cardiology, The First Hospital of Changsha, Changsha, Hunan 410011, P.R. China
Published online on: December 1, 2015 https://doi.org/10.3892/ijmm.2015.2422
Pages: 398-406

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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.

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