Homocysteine Induces Apoptosis of Human Umbilical Vein Endothelial Cells via Mitochondrial Dysfunction and Endoplasmic Reticulum Stress

Figure 7

The diagram of the proposed pathway where Hcy exerts its adverse effect on mitochondrial function and ER stress of the HUVEC. The diagram shows signal transduction events associated with Hcy-induced mitochondrial dysfunction and ER stress. Hcy induces mitochondrial dysfunction including decreased expression of Bcl-2 and MMP and increased mitochondrial ROS causing an increase in the levels of cytoplasmic cytochrome c, cytoplasmic ROS, and caspase-3, which crucially results in HUVEC apoptosis. Simultaneously, Hcy increases expression of GRP78, activates PERK, causes phosphorylation of eIF2α, and finally induces expression of ATF4 and CHOP, thereby partly contributing to HUVEC apoptosis and modulating the activation of NF-κb. In addition, the accumulated cytoplasmic ROS may cause the production of misfolded proteins, thereby triggering the ER stress of HUVEC.