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.