Microcystin-leucine arginine blocks vasculogenesis and angiogenesis through impairing cytoskeleton and impeding endothelial cell migration by downregulating integrin-mediated Rho/ROCK signaling pathway
1.Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, No. 174, Shazheng Street, Shapingba District, Chongqing, 400030, People’s Republic of China ;
Abstract:
The main characteristic of eutrophication is cyanobacteria harmful algae blooms. Microcystin-leucine arginine (MC-LR) is considered to be the most toxic and most commonly secondary metabolite produced by cyanobacteria. It has been reported that MC-LR had potential vascular toxicity. However, the mechanism that MC-LR-induced vascular toxicity is very limited and remains to be clarified. The aim of this study was to evaluate the toxic hazard toward the vasculogenesis and angiogenesis of MC-LR. Its effects on vasculogenesis, sprouting angiogenesis, and endothelial cell tube formation were studied. The study showed that MC-LR exposure blocked vasculogenesis in zebrafish embryos, sprouting angiogenesis from rat aorta, and tube formation of human umbilical vein endothelial cells (HUVECs). In addition, MC-LR exposure also induced the disruption of cytoskeletal structures and markedly inhibited endothelial cell (EC) migration from caudal hematopoietic tissue in zebrafish and HUVEC migration. Western blot analysis showed that MC-LR exposure downregulated the expressions of integrin β1, FAK, Rho, and ROCK. Combined with these results, MC-LR could induce disruption of cytoskeleton via downregulating integrin-mediated FAK/ROCK signaling pathway, leading to the inhibition of EC migration, which finally blocked vasculogenesis and angiogenesis.