Knockdown of miR-665 Protects Against Cardiomyocyte Ischemia/Reperfusion Injury-Induced ROS Accumulation and Apoptosis Through the Activation of Pak1/Akt Signaling in Myocardial Infarction.

In this study, we investigated the function of miR-665 in MI. In the present study, an ischemia/reperfusion (I/R) rat model and a hypoxia/reoxygenation (H/R)-induced H9c2 cell model were successfully established to mimic the MI for in vivo and in vitro studies. The concentrations of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), tumor necrosis factor alpha (TNF-α), IL-6, and reactive oxygen species (ROS) were then measured. Moreover, cell viability and apoptosis were detected by MTT assay, TdT-mediated dUTP nick end labeling (TUNEL), and PI/FITC-annexin V assay. The binding of miR-665 and Pak1 was determined by luciferase assay. miR-665 was upregulated in I/R rats, and the overexpression of miR-665 significantly increased LDH, CK-MB, TNF-α, IL-6, and ROS concentrations and induced cell apoptosis, while knockdown of miR-665 had opposite results. Consistent with in vivo results, miR-665 induced cell apoptosis and ROS generation in H/R-treated H9c2 cells. More importantly, Pak1 was the target gene of miR-665, and knockdown of miR-665 depressed the accumulation of ROS and cell apoptosis by targeting Pak1 and promoting the phosphorylation of Akt, whereas knockdown of Pak1 could attenuate the protection of miR-665 inhibitor in H/R-treated H9c2 cells. Therefore, knockdown of miR-665 protects against cardiomyocyte ischemia/reperfusion injury-induced ROS accumulation and apoptosis through activating Pak1/Akt signaling in MI. In general, understanding the biology and modula...
Source: International Heart Journal - Category: Cardiology Tags: Int Heart J Source Type: research