Epigallocatechin-3-gallate inhibits homocysteine-induced apoptosis of endothelial cells by demethylation of the DDAH2 gene.

Our previous study showed that hypermethylation of dimethylarginine dimethylaminohydrolase 2 contributes to homocysteine-induced apoptosis of human umbilical vein endothelial cells. Epigallocatechin-3-gallate is a green tea-derived phenol which has been proved beneficial on atherosclerosis. It was demonstrated that epigallocatechin-3-gallate inhibits DNA methyltransferase activity and reactivates methylation-silenced genes in cancer cells.

Homocysteine-induced hypermethylation of DDAH2 promoter contributes to apoptosis of endothelial cells.

Homocysteine (Hcy) could induce apoptosis of endothelial cells (ECs). Dimethylarginine dimethylaminohydrolase 2 (DDAH2) is recognized as a protective factor to improve the endothelial function. Defect of DDAH2 has been confirmed to be involved in the Hcy-induced dysfunction of endothelial NO system.

3,4,5,6-Tetrahydroxyxanthone preserves intercellular communication by reduction of the endogenous nitric oxide synthase inhibitor level.

To observe the direct effects of 3,4,5,6-tetrahydroxyxanthone on connexin43 (Cx43) expression in cultured endothelial cells, cells were treated with lysophosphatidylcholine (LPC, 10 mg/l) for 24 h in the presence or absence of different concentrations of 3,4,5,6-tetrahydroxyxanthone (1, 3, or 10 μmol l(- 1)). The reactive oxygen species (ROS) production, cell viability, asymmetric dimethylarginine (ADMA) levels, and Cx43 expression were detected. 3,4,5,6-Tetrahydroxyxanthone significantly inhibited the increase in ROS production and ADMA level, increased cell viability and up-regulated Cx43 mRNA and protein expression induced by LPC.