EGCG attenuates high glucose-induced endothelial cell inflammation by suppression of PKC and NF-κB signaling in human umbilical vein endothelial cells

Abstract

Aims: Vascular inflammation is a key factor in the pathogenesis of diabetes-related vascular complications. Our previous study showed that (-)-epigallocatechin-3-gallate (EGCG) inhibits high glucose-induced vascular smooth muscle cell proliferation, thus it may have beneficial effects in diabetes and its complications. However, the effect of EGCG on inflammation in diabetes is not known. In the present study, we investigated whether EGCG suppresses the vascular inflammation induced by high glucose in human umbilical vein endothelial cells (HUVECs).

Main methods: The inhibitory effect of EGCG on high glucose-induced up-regulation of the expression of vascular cell adhesion molecule 1 (VCAM-1) was measured using enzyme-linked immunosorbent, RT-PCR, immunoblotting and cell adhesion assays. The effect of EGCG on high glucose-induced nuclear factor-kappa B (NF-κB) activation was investigated by immunoblotting, immunofluorescence and electrophoretic mobility shift assays.

Key findings: High glucose increased VCAM-1 expression and enhanced the adhesion of monocytes to HUVECs. Pretreatment with EGCG in a concentration-dependent manner (1.0-50 μM) significantly attenuated these effects. High glucose (25 mM)-mediated vascular inflammation was blocked by PKC pseudosubstrate (PKC inhibitor 19-31) or the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). Stimulation with high glucose increased the NF-κB translocation from the cytoplasm to the nucleus, and increased IκB-α phosphorylation, decreased its expression, and in the presence of EGCG, the effect of high glucose on NF-κB and IκB-α were blocked.

Significance: EGCG suppresses high glucose-induced vascular inflammatory process via the inhibition of PKC and NF-κB activation in HUVECs, suggesting that EGCG may be a potential candidate for the treatment and prevention of diabetic vascular complications.