miR-129 Attenuates Myocardial Ischemia Reperfusion Injury by Regulating the Expression of PTEN in Rats

Abstract

PTEN/AKT signaling plays pivotal role in myocardial ischemia reperfusion injury (MIRI), and miRNAs are involved in the regulation of AKT signaling. This study was designed to investigate the interaction between miR-129 and PTEN in MIRI. A MIRI rat model and a hypoxia reoxygenation (H/R) H9C2 cell model were constructed to simulate myocardial infarction clinically. TTC staining, creatine kinase (CK) activity, TUNEL/Hoechst double staining, Hoechst staining and flow cytometer were used for evaluating myocardial infarction or cell apoptosis. miR-129 mimic transfection experiment and luciferase reporter gene assay were conducted for investigating the function of miR-129 and the interaction between miR-129 and PTEN, respectively. Real-time PCR and western blotting were performed to analyze the gene expression. Compared to the control, MIRI rats presented obvious myocardial infarction, higher CK activity, increased expression of caspase-3 and PTEN, decreased expression of miR-129, and insufficient AKT phosphorylation. Consistently, H/R significantly increased the apoptosis of H9C2 cells, concomitant with the downregulation of miR-129, upregulation of PTEN and caspase-3, and insufficient phosphorylation of AKT, while miR-129 mimic obviously inhibited the expression of PTEN and caspase-3, increased the AKT phosphorylation, and decreased the cell apoptosis. Additionally, miR-129 mimic obviously decreased the relative luciferase activity in H9C2 cells. To our best knowledge, this study firstly found that the low expression of miR-129 accelerates the myocardial cell apoptosis by directly targeting 3 ′ UTR of PTEN. miR-129 is an important biomarker for MIRI, as well as a potential therapy target.

LOXL1-AS1 Aggravates Myocardial Ischemia/Reperfusion Injury Through the miR-761/PTEN Axis

“…Cui et al 28) reported that knocking down PTEN could reduce myocardial pathological damage and inhibit NLRP3-mediated myocardial cell apoptosis. Dai et al 29) reported that miR-129 alleviated MIRI in rats by inhibiting PTEN expression. Through bioinformatics prediction and verification, we noted that miR-761 and PTEN had mutual binding sites.…”

Cardiovascular Disease and miRNAs: Possible Oxidative Stress-Regulating Roles of miRNAs

“…The miRNAs discussed in this section are listed in the following Table 2. Human HF [183] 1 CHF in rats [178] 2 Keap1 [182] Suppressed transcription of Nrf2-dependent antioxidant genes [96] I/R injury in rodents [179][180][181] AngII-induced CM hypertrophy [182] HMGB1 [180] Enhanced HMGB1-mediated NOX activation and subsequent ROS production [157,158] miR-130…”

“…Previous studies have reported that the expression of miR-129 was down-regulated in various experimental models of CVDs, such as CHF [ 178 ], myocardial I/R injury [ 179 , 180 , 181 ], and Ang II-induced CM hypertrophy [ 182 ]. More recently, the down-regulation of miR-129 in the cardiac tissue of patients with heart failure has also been reported [ 183 ].…”