cyanoginosin-lr and Angiodysplasia

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.

Topics: Angiodysplasia; Animals; Apoptosis; Apoptosis Regulatory Proteins; Human Umbilical Vein Endothelial Cells; Humans; Marine Toxins; Microcystins; Mitochondria; Signal Transduction; Vascular Diseases; Zebrafish