Hsa_circ_0007059 promotes apoptosis and inflammation in cardiomyocytes during ischemia by targeting microRNA-378 and microRNA-383.

Circular RNAs (circRNAs) are a class of non-coding RNA molecules that are associated with not only normal physiological functions but also various diseases, including cardiac diseases such as myocardial infarction (MI). The present study explored the potential role of circRNA_0007059 (circ_0007059) during MI pathogenesis using in vitro studies. Microarray and quantitative PCR analyses demonstrated elevated circ_0007059 expression and downregulated miR-378 and miR-383 expression in H2O2-treated mice cardiomyocytes and infarcted hearts of MI mouse model as compared those in relevant controls. Moreover, circ_0007059 knockdown improved cardiomyocyte viability after H2O2 treatment as revealed by the CCK-8 and colony formation assays. Flow cytometry and caspase activity assays demonstrated that circ_0007059 suppressed H2O2-induced cardiomyocyte apoptosis. Enzyme-linked immunosorbent assays and Western blotting revealed that inflammatory cytokine (interleukin-1ß, interleukin-18 and C-C motif chemokine ligand 5) expression was induced by H2O2 treatment and that circ_0007059 repressed H2O2-induced inflammation. Bioinformatics analyses and dual-luciferase reporter assays showed that circ_0000759 acts as a miR-378 and miR-383 sponge. Furthermore, the upregulation or suppression of miR-378 and miR-383 expression in H2O2-treated cardiomyocytes had similar effects on the apoptosis and inflammation of cardiomyocytes as that of circ_0007059 knockdown or overexpression, respectively. Additionally, lentiviral shRNA-circ_0007059 administration to mice with MI considerably reduced the size of infarcted regions and promoted cardiac activity. Collectively, our findings suggest that circ_0007059 expression is upregulated in mice cardiomyocytes in response to oxidative stress and cardiac tissues of MI mouse model, suggesting its involvement in the pathogenesis of MI by targeting miR-378 and miR-383.

Oxidized Low Density Lipoprotein-Induced Atherogenic Response of Human Umbilical Vascular Endothelial Cells (HUVECs) was Protected by Atorvastatin by Regulating miR-26a-5p/Phosphatase and Tensin Homolog (PTEN).

BACKGROUND Atherosclerosis is a chronic and multifactorial disease, and it is the main reason of coronary heart disease, cerebral infarction, and peripheral vascular disease, which leads to the formation of lesions in arterial blood vessels. Our study aimed to explore the protective effect and its underlying mechanism of atorvastatin (ATV) on oxidized low-density lipoprotein (ox-LDL)-induced atherosclerosis. MATERIAL AND METHODS Human umbilical vascular endothelial cells (HUVECs) were cultured and pretreated with ox-LDL to establish an in vitro atherosclerotic cell model. Cell Counting Kit-8 (CCK-8) assay, TUNEL staining, and Transwell assay were used to detect the cell activity, apoptosis, and migration in HUVECs. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were applied to measure the mRNA and protein expressions of adhesion-related genes in HUVECs. RESULTS Pretreated with 100 mg/L ox-LDL resulted in a 57.23% decrease of cell viability and 81.09% increase of apoptotic injury in HUVECs compare to the control. Meanwhile, ox-LDL pretreatment increased the cell migration and the expression of miR-26a-5p in HUVECs. ATV treatment could effectively reverse the cellular damage induced by ox-LDL, decrease the release of adhesion-related molecules, and downregulate the expression of miR-26a-5p by 44.79% in HUVECs. Moreover, phosphatase and tensin homolog (PTEN) was demonstrated to be the target gene of miR-26a-5p. CONCLUSIONS Our results highlight that ATV protects against ox-LDL-induced downregulation of cell viability, upregulation of cell apoptosis, migration, as well as the release of adhesion-related molecules in HUVECs through the miR-26a-5p/PTEN axis. This study provides new insights into the underlying mechanism of ATV therapeutic potential in atherosclerosis, and also provides a new strategy for the treatment of atherosclerosis.

Atorvastatin improves left ventricular remodeling and cardiac function in rats with congestive heart failure by inhibiting RhoA/Rho kinase-mediated endothelial nitric oxide synthase.

The aim of the present study was to investigate the effects and possible mechanisms of atorvastatin (Ato) against chronic heart failure (CHF). A rat model of CHF was established and cardiac functions were assessed using Echocardiography. The expression of RhoA/Rho kinase and endothelial nitric oxide synthase (eNOS) was assessed using western blotting and reverse transcription polymerase chain reaction following 4 weeks of treatment. The three groups assessed in the present study were as follows: The control group (no treatment), the Ato + isopropylnoradrenaline (ISO) group (subcutaneous injections of 340 mg/kg ISO + orally administered 50 mg/kg Ato dissolved in saline; administered once daily) and the ISO group (subcutaneous injections of 340 mg/kg ISO + orally administered with an equal volume of saline; administered once daily). Heart volume and weight in the ISO group were significantly increased compared with the control (C) group (P<0.01), whereas contractility was decreased. The results were reverse for the Ato group when compared with the ISO group (P<0.05). Levels of RhoA/Rho kinase protein and mRNA were significantly increased in the ISO group (P<0.01); however. The mRNA and protein expression of eNOS was significantly decreased (P<0.05) when compared with the C group. The mRNA and protein expression of RhoA/Rho kinase was significantly reduced in the Ato+ISO group compared with the ISO group (P<0.01), whereas the mRNA and protein expression of eNOS was significantly increased (P<0.05). RhoA protein expression was increased in the cytoplasm of the C group and on the cell membrane of the ISO group; however, in the Ato+ISO group, RhoA protein expression on the cell membrane was significantly downregulated when compared with the ISO group (P<0.05). The results of the present study suggest that Ato upregulates eNOS by inhibiting RhoA/Rho kinase overexpression in the myocardial tissue of rats with CHF, thus improving left ventricular remodeling and cardiac function.