Astaxanthin inhibits homocysteine­induced endothelial cell dysfunction via the regulation of the reactive oxygen species­dependent VEGF­VEGFR2­FAK signaling pathway.

Increased plasma levels of homocysteine (Hcy) can cause severe damage to vascular endothelial cells. Hcy­induced endothelial cell dysfunction contributes to the occurrence and development of human cerebrovascular diseases (CVDs). Our previous studies have revealed that astaxanthin (ATX) exhibits novel cardioprotective activity against Hcy­induced cardiotoxicity in vitro and in vivo. However, the protective effect and mechanism of ATX against Hcy­induced endothelial cell dysfunction requires further investigation. In the present study, treatment of human umbilical vascular endothelial cells (HUVECs) with Hcy inhibited the migration, invasive and tube formation potentials of these cells in a dose­dependent manner. Hcy treatment further induced a time­dependent increase in the production of reactive oxygen species (ROS), and downregulated the expression of vascular endothelial growth factor (VEGF), phosphorylated (p)­Tyr­VEGF receptor 2 (VEGFR2) and p­Tyr397­focal adhesion kinase (FAK). On the contrary, ATX pre­treatment significantly inhibited Hcy­induced cytotoxicity and increased HUVEC migration, invasion and tube formation following Hcy treatment. The mechanism of action may involve the effective inhibition of Hcy­induced ROS generation and the recovery of FAK phosphorylation. Collectively, our findings suggested that ATX could inhibit Hcy­induced endothelial dysfunction by suppressing Hcy­induced activation of the VEGF­VEGFR2­FAK signaling axis, which indicates the novel therapeutic potential of ATX in treating Hcy­mediated CVD.