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Caveolae play a role in EGCG‐mediated protection against linoleic acid‐induced endothelial cell activation
Author(s) -
Zheng Yuanyuan,
Lim Eum Jin,
Toborek Michal,
Hennig Bernhard
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.700.7
Subject(s) - caveolae , caveolin 1 , mapk/erk pathway , microbiology and biotechnology , linoleic acid , protein kinase b , endothelial stem cell , signal transduction , p38 mitogen activated protein kinases , chemistry , angiogenesis , protein kinase a , kinase , biology , biochemistry , cancer research , fatty acid , in vitro
Flavonoids can protect against inflammatory diseases such as atherosclerosis by decreasing vascular endothelial cell activation. Plasma microdomains called caveolae are particularly abundant in endothelial cells and play a major role in endothelial trafficking and the regulation of signaling pathways associated with the pathology of vascular diseases. We hypothesize that flavonoids down‐regulate inflammatory parameters by modulating caveolae‐regulated cell signaling. We focused on the role of caveolae and its major protein, caveolin‐1, in mechanisms of linoleic acid‐induced endothelial cell activation and protection by the green tea epigallocatechin gallate (EGCG). Pretreatment with EGCG blocked fatty acid‐induced caveolin‐1, MCP‐1 and COX‐2 expression. Similar results were observed with NF‐kappaB DNA binding activity. Caveolin‐1 silencing blocked linoleic acid‐induced expression of MCP‐1 and COX‐2. Exposure to linoleic acid rapidly increased phosphorylation of several kinases, including p38 MAPK, ERK, and Akt. Inhibitors of ERK and Akt down‐regulated the linoleic acid‐induced increase in COX‐2 protein expression. Our data provide evidence that caveolae may play a critical role in regulating vascular endothelial cell activation and protection by flavonoids such as EGCG. (Supported in part by grants from NIH/NIEHS [P42ES07380] and the University of Kentucky AES.)