Microcystin-LR induces angiodysplasia and vascular dysfunction through promoting cell apoptosis by the mitochondrial signaling pathway.

The harmful algal blooms are becoming increasingly problematic in the regions that drinking water production depends on surface waters. With a global occurrence, microcystins are toxic peptides produced by multiple cyanobacterial genera in the harmful algal blooms. In this study, we examined the effects of microcystin-LR (MC-LR), a representative toxin of the microcystin family, on vascular development in zebrafish and the apoptosis of human umbilical vein endothelial cells (HUVECs). In zebrafish larvae, MC-LR induced angiodysplasia, damaged vascular structures and reduced lumen size at 0.1 μM and 1 μM, leading to the decrease of the blood flow area in the blood vessels and brain hemorrhage, which showed that MC-LR could dose-dependently inhibit vascular development and cause vascular dysfunction. In MC-LR treated HUVECs, the proportion of early apoptosis and late apoptosis cells increased in a concentration-dependent manner. Different concentrations of MC-LR could also activate caspase 3/9 in HUVECs, increase the level of mitochondrial ROS and reduce mitochondrial membrane potential. Additionally, MC-LR could promote the expression of p53 and inhibit the expression of PCNA. The findings showed that MC-LR could promote apoptosis of HUVECs through the mitochondrial signaling pathway. Combined with these results, MC-LR may promote vascular endothelial cell apoptosis through mitochondrial signaling pathway, leading to angiodysplasia and vascular dysfunction.