Underlying mechanism for suppression of vascular smooth muscle cells by green tea polyphenol EGCG released from biodegradable polymers for stent application

Dong Wook Han, Duk Young Jung, Jong Chul Park, Han Hee Cho, Suong Hyu Hyon, Dong Keun Han

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Epigallocatechin-3-O-gallate (EGCG), the predominant catechin from tea, is known to exert a variety of cardiovascular beneficial effects by affecting the activity of receptor and signal transduction kinases. In this study, we investigated the suppressive effects of EGCG released from biodegradable poly(L-lactide-co-ε-caprolactone, PLCL) films on the proliferation, cell cycle progression and matrix metalloproteinase-2 (MMP-2) expression of vascular smooth muscle cells (VSMCs). The involvement of phosphorylated Akt (pAkt) and nuclear factor-IκB (pNF-IκB) as well as the internalization of EGCG into VSMCs was also examined as underlying mechanisms for EGCG-mediated VSMC inhibition. The proliferation of canine aortic SMCs (CASMCs) on EGCG-releasing PLCL (E-PLCL) was significantly inhibited. The culture of CASMCs on E-PLCL resulted in induction of cell cycle arrest at G0/G1 phase and inactivation of pAkt, leading to subsequent apoptosis. Active MMP-2 expression was directly lowered by EGCG released from E-PLCL and indirectly inhibited by the EGCG-mediated suppression of pNF-IκB. We also observed the incorporation of fluorescein isothiocyanate-conjugated EGCG into the cytoplasm of CASMCs and its further nuclear translocation, which could lead to the interruption of the exogenous signals directed to genes responsible for cellular responses of CASMCs. Taken together, the attenuated responses of VSMCs to E-PLCL were shown to be mediated through the suppression of pNF-IκB, pAkt and each subsequent target genes or proteins by EGCG incorporated into the cells.

Original languageEnglish
Pages (from-to)424-433
Number of pages10
JournalJournal of Biomedical Materials Research - Part A
Volume95 A
Issue number2
DOIs
Publication statusPublished - 2010 Nov 1

Fingerprint

Biodegradable polymers
Stents
Polyphenols
Muscle
Cells
Genes
Signal transduction
Cell proliferation
Cell death
Matrix Metalloproteinase 2
Proteins
Tea
epigallocatechin gallate
Catechin
Fluorescein
Phosphotransferases
Apoptosis
Metalloproteases

All Science Journal Classification (ASJC) codes

  • Ceramics and Composites
  • Biomaterials
  • Biomedical Engineering
  • Metals and Alloys

Cite this

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title = "Underlying mechanism for suppression of vascular smooth muscle cells by green tea polyphenol EGCG released from biodegradable polymers for stent application",
abstract = "Epigallocatechin-3-O-gallate (EGCG), the predominant catechin from tea, is known to exert a variety of cardiovascular beneficial effects by affecting the activity of receptor and signal transduction kinases. In this study, we investigated the suppressive effects of EGCG released from biodegradable poly(L-lactide-co-ε-caprolactone, PLCL) films on the proliferation, cell cycle progression and matrix metalloproteinase-2 (MMP-2) expression of vascular smooth muscle cells (VSMCs). The involvement of phosphorylated Akt (pAkt) and nuclear factor-IκB (pNF-IκB) as well as the internalization of EGCG into VSMCs was also examined as underlying mechanisms for EGCG-mediated VSMC inhibition. The proliferation of canine aortic SMCs (CASMCs) on EGCG-releasing PLCL (E-PLCL) was significantly inhibited. The culture of CASMCs on E-PLCL resulted in induction of cell cycle arrest at G0/G1 phase and inactivation of pAkt, leading to subsequent apoptosis. Active MMP-2 expression was directly lowered by EGCG released from E-PLCL and indirectly inhibited by the EGCG-mediated suppression of pNF-IκB. We also observed the incorporation of fluorescein isothiocyanate-conjugated EGCG into the cytoplasm of CASMCs and its further nuclear translocation, which could lead to the interruption of the exogenous signals directed to genes responsible for cellular responses of CASMCs. Taken together, the attenuated responses of VSMCs to E-PLCL were shown to be mediated through the suppression of pNF-IκB, pAkt and each subsequent target genes or proteins by EGCG incorporated into the cells.",
author = "Han, {Dong Wook} and Jung, {Duk Young} and Park, {Jong Chul} and Cho, {Han Hee} and Hyon, {Suong Hyu} and Han, {Dong Keun}",
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Underlying mechanism for suppression of vascular smooth muscle cells by green tea polyphenol EGCG released from biodegradable polymers for stent application. / Han, Dong Wook; Jung, Duk Young; Park, Jong Chul; Cho, Han Hee; Hyon, Suong Hyu; Han, Dong Keun.

In: Journal of Biomedical Materials Research - Part A, Vol. 95 A, No. 2, 01.11.2010, p. 424-433.

Research output: Contribution to journalArticle

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AU - Han, Dong Wook

AU - Jung, Duk Young

AU - Park, Jong Chul

AU - Cho, Han Hee

AU - Hyon, Suong Hyu

AU - Han, Dong Keun

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Y1 - 2010/11/1

N2 - Epigallocatechin-3-O-gallate (EGCG), the predominant catechin from tea, is known to exert a variety of cardiovascular beneficial effects by affecting the activity of receptor and signal transduction kinases. In this study, we investigated the suppressive effects of EGCG released from biodegradable poly(L-lactide-co-ε-caprolactone, PLCL) films on the proliferation, cell cycle progression and matrix metalloproteinase-2 (MMP-2) expression of vascular smooth muscle cells (VSMCs). The involvement of phosphorylated Akt (pAkt) and nuclear factor-IκB (pNF-IκB) as well as the internalization of EGCG into VSMCs was also examined as underlying mechanisms for EGCG-mediated VSMC inhibition. The proliferation of canine aortic SMCs (CASMCs) on EGCG-releasing PLCL (E-PLCL) was significantly inhibited. The culture of CASMCs on E-PLCL resulted in induction of cell cycle arrest at G0/G1 phase and inactivation of pAkt, leading to subsequent apoptosis. Active MMP-2 expression was directly lowered by EGCG released from E-PLCL and indirectly inhibited by the EGCG-mediated suppression of pNF-IκB. We also observed the incorporation of fluorescein isothiocyanate-conjugated EGCG into the cytoplasm of CASMCs and its further nuclear translocation, which could lead to the interruption of the exogenous signals directed to genes responsible for cellular responses of CASMCs. Taken together, the attenuated responses of VSMCs to E-PLCL were shown to be mediated through the suppression of pNF-IκB, pAkt and each subsequent target genes or proteins by EGCG incorporated into the cells.

AB - Epigallocatechin-3-O-gallate (EGCG), the predominant catechin from tea, is known to exert a variety of cardiovascular beneficial effects by affecting the activity of receptor and signal transduction kinases. In this study, we investigated the suppressive effects of EGCG released from biodegradable poly(L-lactide-co-ε-caprolactone, PLCL) films on the proliferation, cell cycle progression and matrix metalloproteinase-2 (MMP-2) expression of vascular smooth muscle cells (VSMCs). The involvement of phosphorylated Akt (pAkt) and nuclear factor-IκB (pNF-IκB) as well as the internalization of EGCG into VSMCs was also examined as underlying mechanisms for EGCG-mediated VSMC inhibition. The proliferation of canine aortic SMCs (CASMCs) on EGCG-releasing PLCL (E-PLCL) was significantly inhibited. The culture of CASMCs on E-PLCL resulted in induction of cell cycle arrest at G0/G1 phase and inactivation of pAkt, leading to subsequent apoptosis. Active MMP-2 expression was directly lowered by EGCG released from E-PLCL and indirectly inhibited by the EGCG-mediated suppression of pNF-IκB. We also observed the incorporation of fluorescein isothiocyanate-conjugated EGCG into the cytoplasm of CASMCs and its further nuclear translocation, which could lead to the interruption of the exogenous signals directed to genes responsible for cellular responses of CASMCs. Taken together, the attenuated responses of VSMCs to E-PLCL were shown to be mediated through the suppression of pNF-IκB, pAkt and each subsequent target genes or proteins by EGCG incorporated into the cells.

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