EGCG protects against oxidized LDL-induced endothelial dysfunction by inhibiting LOX-1-mediated signaling


Ou Hsiu-Chung1,Song Tuzz-Ying2,Yeh Yueh-Chiao3,Huang Chih-Yang45,Yang Shun-Fa6,Chiu Tsan-Hung7,Tsai Kun-Ling8,Chen Kai-Ling1,Wu Yun-Jhen1,Tsai Chiou-Sheng9,Chang Li-Yun10,Kuo Wei-Wen11,Lee Shin-Da112


1. Department of Physical Therapy and Graduate Institute of Rehabilitation Science, China Medical University, Taichung;

2. Department of Nutrition and Health Science, Chungchou Institute of Technology, Changhwa;

3. Graduate Institute of Natural Healing Sciences, Nanhua University, Chiayi;

4. Graduate Institute of Basic Medical Science, China Medical University, Taichung;

5. Department of Health and Nutrition Biotechnology, Asia University, Taichung;

6. Institute of Medicine, Chung Shan Medical University, Taichung;

7. Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung;

8. Graduate Institute of Clinical Medical Science, China Medical University, Taichung;

9. Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung;

10. Graduate Institute of Molecular Systems Biomedicine,

11. Department of Biotechnology, China Medical University, Taichung; and

12. Department of Healthcare Administration, Asia University, Taichung, Taiwan


Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), originally identified as the major receptor for oxidized low-density lipoprotein (oxLDL) in endothelial cells, plays a major role in the pathology of vascular diseases. Green tea consumption is associated with reduced cardiovascular mortality in some epidemiological studies. In the present study, we hypothesized that the most abundant polyphenolic compound in tea, epigallocatechin-3-gallate (EGCG), can downregulate parameters of endothelial dysfunction by modulating LOX-1-regulated cell signaling. In cultured human umbilical vein endothelial cells (HUVECs), exposure to oxLDL (130 μg/ml), which led to an increase in LOX-1 expression at the RNA and protein levels, was abrogated by addition of EGCG or DPI, a well-known inhibitor of flavoproteins, suggesting the involvement of NADPH oxidase. Furthermore, oxLDL rapidly activated the membrane translocation of Rac-1 and p47phoxand the subsequent induction of ROS generation, which was suppressed markedly by pretreatment with EGCG or anti-LOX-1 monoclonal antibody. OxLDL also increased p38 MAPK phosphorylation and decreased phosphorylation of the amino-terminal region of Akt, with maximal induction at about 30 min, and NF-κB phosphorylation within 1 h, resulting in redox-sensitive signaling. In addition, oxLDL diminished the expression of endothelial nitric oxide synthase (eNOS), enhanced the expression of endothelin-1 and adhesion molecules (ICAM, E-selectin, and monocyte chemoattractant protein-1), and increased the adherence of monocytic THP-1 cells to HUVECs. Pretreatment with EGCG, however, exerted significant cytoprotective effects in all events. These data suggest that EGCG inhibits the oxLDL-induced LOX-1-mediated signaling pathway, at least in part, by inhibiting NADPH oxidase and consequent ROS-enhanced LOX-1 expression, which contributes to further ROS generation and the subsequent activation of NF-κB via the p38 MAPK pathway. Results from this study may provide insight into a possible molecular mechanism by which EGCG suppresses oxLDL-mediated vascular endothelial dysfunction.


American Physiological Society


Physiology (medical),Physiology

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