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-κB (pNF-κB) 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 G(0)/G(1) 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-κB. 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-κB, pAkt and each subsequent target genes or proteins by EGCG incorporated into the cells