Microcystin-leucine arginine exhibits adverse effects on human aortic vascular smooth muscle cells in vitro

Abstract

Microcystin-leucine arginine (MC-LR) is a kind of toxin produced by cyanobacteria, which can do harm to human and livestock health. MC-LR can easily enter tissues and organs through the blood circulation and accumulate in certain target organs. Vessels are prone to contact with MC-LR during growth and development. Previous study had demonstrated that MC-LR had potential vascular toxicity. However, it is not clear whether MC-LR has adverse effects on vascular smooth muscle cells. In this study, we evaluated the cytotoxicity of MC-LR exposure (0.01, 0.05, 0.1, 0.5, and 1 μM) on human aortic vascular smooth muscle cells (HAVSMCs) in vitro. The data showed that MC-LR exposure inhibited the HAVSMC proliferation and migration, induced HAVSMC apoptosis, cytoskeleton destruction, S-phase arrest, mitochondrial transmembrane potential (MMP) loss, and reactive oxygen species (ROS) production. In addition, MC-LR exposure resulted in the imbalance between oxidants and antioxidants, increased the caspase-3 and caspase-9 activities, and down-regulated the gene expressions (integrin β1, Rho, ROCK, MLC). Taken together, MC-LR could induce the generation of ROS in HAVSMCs, leading to apoptosis by the mitochondrial signaling pathway. MC-LR could also induce cytoskeletal disruption by integrin-mediated FAK/ROCK signaling pathway, leading to cell cycle arrest and the inhibition of HAVSMCs proliferation and migration. The current findings facilitate an understanding of the mechanism of MC-LR toxicity involved in angiocardiopathy.