Spiromesifen contributes vascular developmental toxicity via disrupting endothelial cell proliferation and migration in zebrafish embryos
2022
Wang, Mingxing | Liu, Juan | Wang, Huiyun | Hu, Tingzhang
Spiromesifen (SPF) is a specific contact pesticide, which has been widely used to control the growth of sucking insects like mites and whiteflies on crops. Although its residues in crops and effects on organisms has been extensively reported, its impact on the vasculature is still not being reported. In the present study, using human umbilical vein endothelial cells (HUVECs) and zebrafish embryos, we investigated the effects of SPF on blood vessel development and its mechanism of action. SPF exposure triggered abnormal blood vessel development, including vascular deletions and malformations, inhibition of CCV remodeling, and decrease of SIV areas. SPF exposure also obstructed the migration of endothelial cell from caudal hematopoietic tissue in zebrafish embryos. SPF damaged cytoskeleton, caused cell cycle arrest, inhibited the viability and migration of HUVECs. In addition, SPF also inhibited the expression of the VEGF/VEGFR pathway-related genes (hif1a, vegfa, flt1, and kdrl), cell cycle-related genes (ccnd1, ccne1, cdk2, and pcna), and Rho/ROCK pathway-related genes (itgb1, rho, rock, mlc-1, and vim-1). Taken together, SPF may inhibit the proliferation and migration of vascular endothelial cells through disturbing cytoskeleton via the Rho/ ROCK pathway, resulting in vascular malformation. Our study contributes to potential insight into the mechanism of SPF toxicity in angiocardiopathy.
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