CircRNA Is Involved In Vascular Endothelial Injury And Its Mechanism Under Impinging Flow

The mechanism of formation of intracranial aneurysms(IA)remains unclear.Vascular endothelial damage caused by hemodynamic factors is considered to be an important factor in its formation and development.Circular RNA(circRNA)a new type of special type of non-coding RNA that plays a regulatory role in gene signaling pathways.To elucidate the effects of hemodynamics on the function of vascular endothelial cells(ECs),we used a "T" flow chamber system designed by ourselves to simulate the hemodynamic environment at the arterial bifurcation for experiments to impinging cells.A high-throughput circular RNA microarray chip was used to analyze the differential expression profiles of circular RNA in ECs before and after impinging flow at a flow rate of 500 mL / min.The characteristics of differentially expressed circular RNA were analyzed by bioinformatics means,and the chip results were verified by RT-qPCR.Bioinformatics target analysis was used to predict the cellular regulatory pathways involved in the differential expression of circular RNA,construct a regulatory network,and verify the interrelationship between the nodes by RT-qPCR,western blot and luciferase experiments.The expression of many circular RNAs in ECs changed after impinging flow.A total of 974 differential expressions(FC≥2 and P<0.05)were found,of which 378 were up-regulated and 596 were down-regulated.GO enrichment analysis and pathway analysis suggest that these differentially expressed circular RNAs may be involved in the migration,inflammation,injury and apoptosis of ECs.Bioinformatics analysis and target prediction of circRNA suggest that hsa-circ-0049241-miR-221-3p-ICAM-1 pathway may be involved in the regulation of hemodynamic-induced vascular endothelial cell injury.RT-qPCR and western blot preliminarily verified that the expression differences of the nodes in the pathway were consistent with the relationship between pathway regulation.However,further luciferase experiments have not confirmed the existence of an interaction binding site between hsa-circ-0049241 and miR-221-3p.CircRNA may be involved in the regulation of hemodynamic vascular endothelial cell injury,but the specific regulatory pathway remains to be further studied.