摘要SARS-CoV-2 can encode circular RNAs(circRNAs);however,the potential effects of exogenous SARS-CoV-2 circRNAs on cardiovascular sequelae remain unknown.Three circRNAs derived from the nucleocapsid(N)gene of SARS-CoV-2,namely,circSARS-CV2-Ns,were identified for functional studies.In particular,circSARS-CV2-N1368 was shown to enhance platelet adhesiveness to endothelial cells(ECs)and inhibit EC-dependent vascular relaxation.Moreover,exogenous expression of circSARS-CV2-N1368 suppressed EC proliferation and migration and decreased angiogenesis and cardiac organoid beating.Mechanistically,we elucidated that circSARS-CV2-N1368 sponged the microRNA miR-103a-3p,which could reverse circSARS-CV2-N1368-induced EC damage.Additionally,activating transcription factor 7(ATF7)was identified as a target gene of miR-103a-3p,and Toll-like receptor 4(TLR4)was verified as a downstream gene of ATF7 that mediates circARS-CV2-N1368-induced activation of nuclear factor kappa B(NF-κB)signaling and ROS production in ECs.Importantly,the reactive oxygen species(ROS)scavenger NAC mitigated the circSARS-CV2-N1368-promoted EC impairment.Our findings reveal that the TLR4/NF-κB/ROS signal pathway is critical for mediating circSARS-CV2-N1368-promoted oxidative damage in ECs,providing insights into the endothelial impairment caused by circSARS-CV2-Ns.