Overexpression of micro<scp>RNA</scp>‐99a attenuates heart remodelling and improves cardiac performance after myocardial infarction

Zhang

et al. 2017

Cell Physiol Biochem

Background/Aims: Myocardial infarction (MI) is a leading cause of morbidity and mortality. Here, we sought to explore the potential role and underlying mechanism of miR-145 in MI. Methods: H9c2 cells were cultured under persistent hypoxia to simulate MI. The hypoxia-induced injury was assessed on the basis of cell viability, migration, invasion and apoptosis. The expression of miR-145 was evaluated by qRT-PCR and the influence of aberrantly expressed miR-145 on H9c2 cells under hypoxia was also estimated. Utilizing bioinformatics methods, the target genes of miR-145 were verified by luciferase reporter assay. Then, effects of abnormally expressed target gene on miR-145 silenced H9c2 cells were assessed. Finally, the phosphorylation levels of key kinases in the phosphatidylinositol-3-kinase (PI3K)/AKT and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways were detected by Western blot analysis. Results: Hypoxia remarkably lowered viability, migration and invasion but promoted cell apoptosis. Meantime, the miR-145 level was up-regulated in H9c2 cells under hypoxia. Following experiments suggested that hypoxia-induced injury was exacerbated by miR-145 overexpression while was alleviated by miR-145 silence. Rac1 was predicted and further validated to be a target gene of miR-145. The influence of miR-145 silencing on H9c2 cells under hypoxia could be reversed by down-regulation of Rac1. Additionally, the phosphorylation levels of PI3K, AKT, MAPK and ERK were all elevated in miR-145 silenced cells and these alterations were reversed by down-regulation of Rac1. Conclusion: miR-145 silencing could protect H9c2 cells against hypoxia-induced injury by targeting Rac1, in which PI3K/AKT and MAPK/ERK pathways might be involved.

Section: Introductionmentioning

confidence: 99%

MicroRNA-145 Aggravates Hypoxia-Induced Injury by Targeting Rac1 in H9c2 Cells

Zhang

et al. 2017

Cell Physiol Biochem

“…These findings are consistent with a former study on the protective role of miR-99 against cardiomyocyte apoptosis. 17) Thus, miR-99a has protective effects against cardiomyocyte oxidative injury.…”

Section: Discussionmentioning

confidence: 99%

“…15,16) However, in a model of myocardial infarction, miR-99a has been revealed to inhibit cardiomyocyte apoptosis, suggesting a cardioprotective role for miR-99a. 17) These studies lead us to speculate about the role of miR-99a in oxidative injury during cardiovascular disease, however, little has been reported in previous studies.…”

Section: Editorial P310mentioning

confidence: 99%

microRNA-99a Reduces Lipopolysaccharide-Induced Oxidative Injury by Activating Notch Pathway in H9c2 Cells

et al. 2017

SummarymicroRNA-99a (miR-99a) is recently recognized as a key regulator in various cancers and cardiovascular diseases. In the present study, we sought to investigate the effects of miR-99a in rat cardiomyocyte H9c2 cells against oxidative injury induced by lipopolysaccharide (LPS).MTT assay, reactive oxygen species (ROS) assay, flow cytometry and lactate dehydrogenase (LDH) assay were respectively used to explore viability, ROS levels, apoptosis, and cell death in H9c2 cells. Quantitative PCR (qRT-PCR) was performed to confirm the expression of miR-99a. Western blot was performed to determine the expression of Notch pathway factors.LPS could significantly suppress viability and increase cell death, apoptosis, and ROS level (P < 0.05). However, miR-99a could significantly increase the viability and decrease apoptosis and ROS level of H9c2 cells (P < 0.05). Overexpression of miR-99a could activate a Notch pathway and regulate the expression of B-cell CLL/lymphoma 2 (BCL2) and cleaved caspase 3.Our study found that overexpression of miR-99a could attenuate LPS-induced oxidative injury in H9c2 cells, possibly via a Notch pathway. These findings suggest that miR-99a may be a key factor in cardiomyocyte oxidative injury and could be a new therapeutic strategy for cardiovascular diseases. (Int Heart J 2017; 58: 422-427)

“…Searching for direct target genes of miR-99a in cardiomyocytes will advance our understanding of the mechanisms whereby miR-99a protects cardiomyocytes from oxidative injury. Recent studies demonstrated that overexpression of miR-99a in murine hearts using a lentiviral vector attenuated left ventricular remodeling after myocardial infarction, 30) and cardiac hypertrophy induced by transverse aortic constriction. 31) Further studies are necessary to determine whether overexpression of miR-99a also attenuates LPS-induced myocardial oxidative injury and dysfunction without altering physiological ROS signaling in a A number of miRNAs have been identified that are expressed in cardiac tissue and thus likely to play a key role in cardiac physiology and pathophysiology.…”

Section: Article P422mentioning

confidence: 99%

MicroRNA-99a

Liu

Akazawa

2017

Int. Heart J.

R eactive oxygen species (ROS) are continuously formed in myocardium as a byproduct of mitochondrial oxidative phosphorylation, and are also produced by several enzymes such as NADPH oxidases, xanthine oxidase, and uncoupled endothelial NO synthase.1,2) In normal cardiovascular physiology, ROS act as essential signaling molecules that modulate the activity of many bioactive molecules including protein kinases, phosphatases, transcription factors, and cytoskeletal proteins.3) However, excessive and aberrant production of ROS during pathological oxidative stress can cause cellular dysfunction and death by inducing irreversible damage of organelles and macromolecules such as lipids, proteins, and DNA.1,2) An increasing body of evidence has suggested that oxidative stress is crucially involved in the pathogenesis and progression of a wide range of cardiovascular diseases.1,2) For example, it was reported that the myocardial ROS levels were elevated in animal models of ischemia-reperfusion injury 2,4) and heart failure, 5) and that a number of antioxidant strategies using ROS scavengers provided cardioprotection in these animal models.2) However, clinical interventions by treatment with antioxidants have proven to be ineffective or even harmful for patients with cardiovascular diseases.2,6) Rather than simple antioxidant strategies, a strategy to reduce pathological oxidative stress without altering physiological ROS signaling will put forward the translation of ROS modulation into the clinic. 7)