Role of caveolin-1 in EGCG-mediated protection against linoleic-acid-induced endothelial cell activation

Yuanyuan Zheng, Eum Jin Lim, Lei Wang, Eric J. Smart, Michal Toborek, Bernhard Hennig

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Flavonoids can protect against inflammatory diseases such as atherosclerosis by decreasing vascular endothelial cell activation. Plasma microdomains called caveolae may be critical in regulating endothelial activation. 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 can down-regulate endothelial 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 catechin epigallocatechin-3-gallate (EGCG). Exposure to linoleic acid for 6 h induced expression of both caveolin-1 and cyclooxygenase (COX)-2. Pretreatment with EGCG blocked fatty-acid-induced caveolin-1 and COX-2 expression in a time- and concentration-dependent manner. Similar results were observed with nuclear factor-kappa B DNA binding activity, which was also reduced by caveolin-1 silencing. Exposure to linoleic acid rapidly increased phosphorylation of several kinases, including p38 MAPK, extracellular signal regulated kinase 1/2 (ERK1/2) and amino kinase terminal (Akt), with maximal induction at about 10 min. Inhibitors of ERK1/2 and Akt down-regulated the linoleic-acid-induced increase in COX-2 protein, which also occurred after pretreatment with EGCG. Caveolin-1 silencing blocked linoleic-acid-induced phosphorylation of ERK1/2 and protein expression of COX-2, suggesting that specific MAPK signaling is caveolae dependent. Our data provide evidence that caveolae may play a critical role in regulating vascular endothelial cell activation and protection by flavonoids such as EGCG.

Original languageEnglish
Pages (from-to)202-209
Number of pages8
JournalJournal of Nutritional Biochemistry
Issue number3
StatePublished - Mar 2009

Bibliographical note

Funding Information:
This research was supported in part by grants from NIEHS, NIH (P42ES07380) and the University of Kentucky AES.


  • Caveolae
  • Cell signaling
  • EGCG
  • Endothelial cell
  • Flavonoids
  • Inflammation
  • Linoleic acid
  • Protection

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry


Dive into the research topics of 'Role of caveolin-1 in EGCG-mediated protection against linoleic-acid-induced endothelial cell activation'. Together they form a unique fingerprint.

Cite this