The main objective of the article was to explore the role of circ_0091761 in acute myocardial infarction (AMI)-induced endothelial injury.A cellular model of AMI was constructed by hypoxia-induced HUVECs. miRNAs that may interact with circ_0091761 were recognized by the ENCORI and circular RNA Interactom databases. RT-qPCR was performed to analyze the levels of circ_0091761 in AMI patients as well as miR-1278, ICAM1, and VCAM1 in hypoxia-induced HUVECs. Flow cytometry was used to detect apoptosis. ROS kit and LDH kit were used to detect the levels of ROS and LDH, respectively. Dual-luciferase reporter assay, RIP assay, and RNA pull-down assay were performed to validate their interaction between circ_0091761 and miR-1278.circ_0091761 was elevated in AMI patients compared to healthy controls. Silencing circ_0091761 reduced apoptosis, ICAM1, and VCAM1 levels, as well as ROS and LDH. circ_0091761 could interact with miR-1278 and negatively regulate miR-1278 expression in hypoxia-induced HUVECs. At the same time, inhibiting miR-1278 reverses the protective effect of transfected si-circ_0091761 on HUVECs.Down-regulation of circ_0091761 ameliorates AMI-induced endothelial injury by targeting miR-1278.Not applicable.© 2025. The Author(s).