2B.06: EPIGALLOCATECHIN-3-GALLATE ATTENUATES URIC ACID-INDUCED INFLAMMATORY RESPONSES AND OXIDATIVE STRESS BY MODULATING NOTCH PATHWAY

• Published in: Journal of hypertension Vol. 33 Suppl 1 - ESH 2015 Abstract Book; no. Supplement 1; p. e23
• Main Authors: Xie, H, Sun, J, Chen, Y, Zong, M, Li, S, Wang, Y
• Format: Journal Article
• Language: English
• Published: England Copyright Wolters Kluwer Health, Inc. All rights reserved 01-06-2015
• ISSN: 0263-6352; 1473-5598
• DOI: 10.1097/01.hjh.0000467411.86784.c1

OBJECTIVE:Hyperuricemia is recently reported to play a role in hypertension, metabolic syndrome and vascular damage. (-)-Epigallocatechin-3-Gallate (EGCG) is a major polyphenol component of green tea with potent antiinflammatory and antioxidant effects. The aim of this study was to further investigate whether EGCG can prevent the UA-induced inflammatory effect of Human Umbilical Vein Endothelial Cells (HUVEC) and the involved mechanisms in vitro.(Figure is included in full-text article.)
DESIGN AND METHOD:HUVEC were subjected to the action of 8 mg/dl uric acid (UA) with or without 20 μM EGCG treatment. RT-PCR and western blots were performed to determine the level of the inflammation markers. The antioxidant activity was evaluated by measuring scavenged reactive oxygen species (ROS). Functional studies of the role of Notch-1 in HUVEC cell lines were performed using RNA interference analyses. The full cDNA of Notch-1 was cloned in the pcDNA3.1 vector and transfected in HUVEC cells.
RESULTS:UA significantly increased the expression of IL-6, ICAM-1, TNF-α, MCP-1, and the production of ROS in HUVEC cells. Meanwhile, the expression of Notch-1 and its downstream proteins significantly increased. The inhibition of Notch-1 signaling using siRNA considerably impeded the expression of inflammatory cytokines under the treatment by UA. Interestingly, EGCG substantially suppressed the expression of inflammatory cytokines through Notch-1 signal pathways and hindered the generation of ROS.
CONCLUSIONS:Taken together, our findings indicated that Notch-1 played an important role in the UA-induced inflammatory response, and the downregulation of Notch-1 by EGCG could be an effective approach to decrease the inflammation and oxidative stress induced by UA.