(-)-epigallocatechin gallate inhibits endothelin-1-induced C-reactive protein production in vascular smooth muscle cells

Basic Clin Pharmacol Toxicol. 2010 Aug;107(2):669-75. doi: 10.1111/j.1742-7843.2010.00557.x. Epub 2010 Mar 22.

Abstract

Numerous studies have shown that C-reactive protein (CRP), a pro-inflammation cytokine, makes a direct contribution to atherosclerosis, and that (-)-epigallocatechin gallate (EGCG) is able to exert an anti-atherosclerotic effect by anti-oxidative and anti-inflammatory activities. Based on our previous study, the effect of EGCG on endothelin-1 (ET-1)-induced CRP production in rat vascular smooth muscle cells (VSMCs) and the possible mechanism were observed. The in vitro experiments showed that EGCG concentration-dependently inhibited ET-1-stimulated expression of CRP both in protein and mRNA levels in VSMCs as determined by the immunocytochemical staining, the enzyme-linked immunosorbent assay and the real-time quantitative polymerase chain reaction (RT-qPCR). The in vivo investigation with the double-labelled immunofluorescence staining and RT-qPCR displayed that EGCG also prevented ET-1-induced CRP expression in protein and mRNA levels in the aortic VSMCs of rats receiving the subchronic infusion of ET-1. In addition, EGCG suppressed reactive oxygen species (ROS) generation evoked by ET-1 in VSMCs as observed by the fluorescence probe. These demonstrate that EGCG may inhibit ET-1-stimulated generation of CRP in VSMCs so to relieve the inflammatory response and oxidative stress via blocking ROS signal, which provides new evidence for an anti-atherosclerotic effect of EGCG.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Aorta, Thoracic / cytology
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism*
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cells, Cultured
  • Endothelin-1 / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression / drug effects
  • Male
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Antioxidants
  • Endothelin-1
  • RNA, Messenger
  • Reactive Oxygen Species
  • Catechin
  • C-Reactive Protein
  • gallocatechol