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EGCG protects against oxidized LDL-induced endothelial dysfunction by inhibiting LOX-1-mediated signaling.
J Appl Physiol (1985). 2010 Jun; 108(6):1745-56.JA

Abstract

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 microg/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 p47phox and 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-kappaB 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-kappaB 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.

Authors+Show Affiliations

Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, and Department of Obstetrics and Gynecology, China Medical University Hospital, 91 Hsueh-Shih Road, Taichung 40202, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20203069

Citation

Ou, Hsiu-Chung, et al. "EGCG Protects Against Oxidized LDL-induced Endothelial Dysfunction By Inhibiting LOX-1-mediated Signaling." Journal of Applied Physiology (Bethesda, Md. : 1985), vol. 108, no. 6, 2010, pp. 1745-56.
Ou HC, Song TY, Yeh YC, et al. EGCG protects against oxidized LDL-induced endothelial dysfunction by inhibiting LOX-1-mediated signaling. J Appl Physiol (1985). 2010;108(6):1745-56.
Ou, H. C., Song, T. Y., Yeh, Y. C., Huang, C. Y., Yang, S. F., Chiu, T. H., Tsai, K. L., Chen, K. L., Wu, Y. J., Tsai, C. S., Chang, L. Y., Kuo, W. W., & Lee, S. D. (2010). EGCG protects against oxidized LDL-induced endothelial dysfunction by inhibiting LOX-1-mediated signaling. Journal of Applied Physiology (Bethesda, Md. : 1985), 108(6), 1745-56. https://doi.org/10.1152/japplphysiol.00879.2009
Ou HC, et al. EGCG Protects Against Oxidized LDL-induced Endothelial Dysfunction By Inhibiting LOX-1-mediated Signaling. J Appl Physiol (1985). 2010;108(6):1745-56. PubMed PMID: 20203069.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - EGCG protects against oxidized LDL-induced endothelial dysfunction by inhibiting LOX-1-mediated signaling. AU - Ou,Hsiu-Chung, AU - Song,Tuzz-Ying, AU - Yeh,Yueh-Chiao, AU - Huang,Chih-Yang, AU - Yang,Shun-Fa, AU - Chiu,Tsan-Hung, AU - Tsai,Kun-Ling, AU - Chen,Kai-Ling, AU - Wu,Yun-Jhen, AU - Tsai,Chiou-Sheng, AU - Chang,Li-Yun, AU - Kuo,Wei-Wen, AU - Lee,Shin-Da, Y1 - 2010/03/04/ PY - 2010/3/6/entrez PY - 2010/3/6/pubmed PY - 2010/10/12/medline SP - 1745 EP - 56 JF - Journal of applied physiology (Bethesda, Md. : 1985) JO - J Appl Physiol (1985) VL - 108 IS - 6 N2 - 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 microg/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 p47phox and 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-kappaB 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-kappaB 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. SN - 1522-1601 UR - https://www.unboundmedicine.com/medline/citation/20203069/EGCG_protects_against_oxidized_LDL_induced_endothelial_dysfunction_by_inhibiting_LOX_1_mediated_signaling_ L2 - https://journals.physiology.org/doi/10.1152/japplphysiol.00879.2009?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -