title: Epigallocatechin-3-gallate is a potent phytochemical inhibitor of intimal hyperplasia in the wire-injured carotid artery.
abstract: OBJECTIVE
  Epigallocatechin-3-gallate (EGCG), a catechin gallate ester, is the major component of green tea and has been demonstrated to inhibit tumor growth as well as inhibit smooth muscle cell migration. We evaluated the effect of the phytochemicals resveratrol, allicin, sulforaphane (SFN), and EGCG on intimal hyperplasia in the carotid artery injury model.
  
  
  METHODS
  Intimal hyperplasia was induced in carotid arteries of adult Sprague-Dawley rats with a wire injury. Experimental animals received intraperitoneal injections of one of the four phytochemicals daily beginning 1 day prior to surgery and continued for up to 4 weeks. Control animals were administered saline. Carotid specimens were harvested at 2 weeks and subjected to quantitative image analysis. In addition, EGCG specimens were analyzed for cell proliferation, immunohistochemistry, and Western blot analysis.
  
  
  RESULTS
  Quantitative image analysis showed significant phytochemical suppression of intimal hyperplasia at 2 and 4 weeks postoperatively with EGCG (62% decrease in intimal area). Significant decreases were also noted at 2 weeks for SFN (56%) and resveratrol (44%), whereas the decrease with allicin (24%) was not significant. Quantification of intimal hyperplasia by intima:media ratio showed similar results. Cell proliferation assay of specimens demonstrated suppression by EGCG. Immunohistochemical staining of EGCG-treated specimens showed extracellular signal-regulated kinase (ERK) suppression but not of the c-jun N-terminal kinase or p38 pathways. Western blot analysis confirmed reduced ERK activation in arteries treated with EGCG.
  
  
  CONCLUSIONS
  Intraperitoneal injection of the phytochemicals EGCG, SFN, resveratrol, and allicin have suppressive effects on the development of intimal hyperplasia in the carotid artery injury model, with maximal effect due to EGCG. The mechanism of EGCG action may be due to inhibition of ERK activation. EGCG may affect a common pathway underlying either neoplastic cellular growth or vascular smooth muscle cellular proliferation.
authors.affiliation: Department of Vascular Surgery, Englewood Hospital, Englewood, NJ.
authors.forename: Vicente
authors.initials: V
authors.lastname: Orozco-Sevilla
authors.forename: Rotem
authors.initials: R
authors.lastname: Naftalovich
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoffmann
authors.forename: Dennis
authors.initials: D
authors.lastname: London
authors.forename: Eric
authors.initials: E
authors.lastname: Czernizer
authors.forename: Chenzi
authors.initials: C
authors.lastname: Yang
authors.forename: Alan
authors.initials: A
authors.lastname: Dardik
authors.forename: Herbert
authors.initials: H
authors.lastname: Dardik
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000494:pharmacology*; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004220:Disulfides; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006965:Hyperplasia; D007274:Injections, Intraperitoneal; D017879:Isothiocyanates / Q000494:pharmacology; D008297:Male; D058426:Neointima; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D013441:Sulfinic Acids / Q000494:pharmacology; D013454:Sulfoxides; D013997:Time Factors
chemical_list: D002317:Cardiovascular Agents; D004220:Disulfides; D017879:Isothiocyanates; D047428:Protein Kinase Inhibitors; D013267:Stilbenes; D013441:Sulfinic Acids; D013454:Sulfoxides; C006452:allicin; D002392:Catechin; C045651:epigallocatechin gallate; D048049:Extracellular Signal-Regulated MAP Kinases; C016766:sulforaphane; D000077185:Resveratrol
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