Downregulation of folate receptor α contributes to homocysteine-induced human umbilical vein endothelial cell injury via activation of endoplasmic reticulum stress.

Elevated plasma homocysteine (Hcy) levels are associated with endothelial dysfunction. Previous studies have indicated the role of endoplasmic reticulum (ER) stress in Hcy-induced endothelial injury. However, the mechanism of action remains unclear. In the current study, the role of human folate receptor α (hFRα) in Hcy-induced ER stress was investigated, along with endothelial injury in human umbilical vein endothelial cells (HUVECs). The results showed that a moderate dose of Hcy induced morphological injury and reduced viability of HUVECs. Furthermore, moderate-dose Hcy reduced hFRα expression in HUVECs. Notably, hFRα inhibition by RNA interference resulted in activation of the protein kinase RNA-like endoplasmic reticulum kinase pathway and increased apoptosis of HUVECs. In conclusion, this study demonstrated the presence of hFRα in HUVECs, and indicated its role in the regulation of ER stress and cell injury by Hcy. [ABSTRACT FROM AUTHOR]