Salvianolic Acid B Protects Cardiomyocytes from Ischemia/Reperfusion Injury by Mediating circTRRAP/miR-214-3p/SOX6 Axis

Abstract

Circular RNAs (circRNAs) are a class of powerful regulators of gene expression. This study aimed to determine whether circTRRAP (hsa_circ_0081241) was implicated in the cardioprotective effects of salvianolic acid B (Sal B) against myocardial ischemia/reperfusion (I/R) injury and its associated mechanism.Cell viability was analyzed using Cell Counting Kit-8 (CCK-8), and flow cytometry was conducted to evaluate cell cycle progression and cell apoptosis. The leakage of lactic dehydrogenase (LDH), production of malondialdehyde (MDA), and activity of superoxide dismutase (SOD) were measured using their corresponding commercial kits to analyze cell death and oxidative stress.I/R treatment suppressed viability and cell cycle progression and induced the apoptosis and oxidative stress of AC16 cardiomyocytes, whereas Sal B protected AC16 cardiomyocytes against I/R injury. I/R upregulated circTRRAP expression, whereas Sal B dose-dependently reduced the circTRRAP level in AC16 cardiomyocytes. The protective effects of Sal B in I/R-induced AC16 cardiomyocytes were overturned by the overexpression of circTRRAP. CircTRRAP negatively regulated miR-214-3p expression by binding to it in AC16 cardiomyocytes. The circTRRAP overexpression-mediated effects were reversed by the addition of miR-214-3p mimics in AC16 cardiomyocytes. MiR-214-3p targeted the 3'-untranslated region (3'UTR) of SOX6, and SOX6 was regulated by the circTRRAP/miR-214-3p axis in AC16 cardiomyocytes. SOX6 knockdown overturned the circTRRAP overexpression-induced effects in AC16 cardiomyocytes.In conclusion, the silence of circTRRAP was implicated in Sal B-mediated cardioprotective effects against I/R injury by regulating the miR-214-3p/SOX6 axis.