Tanshinone IIA attenuates ox‐LDL‐induced endothelial cell injury by inhibiting NF‐kapaB pathway via circ_0000231/miR‐590‐5p/TXNIP axis

Abstract

Tanshinone IIA (TSIIA) exhibits inhibitory function in atherosclerosis (AS) progression, and circular RNAs (circRNAs) are pivotal regulators in AS. However, the relation between TSIIA and circ_0000231 in AS pathogenesis remains unknown. In this study, oxidized low‐density lipoprotein (ox‐LDL) was used to establish AS cell model. Treatment of ox‐LDL inhibited cell growth but promoted apoptosis, inflammation, and oxidative stress. Then, TSIIA was shown to attenuate ox‐LDL‐induced endothelial injury. Furthermore, the protective effect of TSIIA against ox‐LDL‐induced endothelial cell injury was reversed by circ_0000231. Circ_0000231 was identified as a miR‐590‐5p sponge. Also, miR‐590‐5p downregulation restored the protection of TSIIA for endothelial cell function. Moreover, circ_0000231 was found to upregulate thioredoxin interacting protein (TXNIP) level via targeting miR‐590‐5p. TXNIP overexpression mitigated the regulatory function of circ_0000231 knockdown after co‐treatment with ox‐LDL and TSIIA. TXNIP upregulation recovered the inhibitory regulation of TSIIA in ox‐LDL‐induced cell damage. In addition, TSIIA inactivated NF‐kapaB (NF‐κB) signaling pathway via regulating miR‐590‐5p/TXNIP axis by downregulating circ_0000231. All these results suggested that TSIIA inhibited ox‐LDL‐induced AS progression in endothelial cells by affecting NF‐κB pathway via circ_0000231/miR‐590‐5p/TXNIP.