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      miR-190-5p Alleviates Myocardial Ischemia-Reperfusion Injury by Targeting PHLPP1

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      1 , 1 , 1 , 1 , 2 ,

      Disease Markers

      Hindawi

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          Abstract

          Objective

          Myocardial ischemia-reperfusion (I/R) injury (MIRI) refers to the more serious myocardial injury after blood flow recovery, which seriously affects the prognosis of patients with ischemic cardiomyopathy. This study explored the new targets for MIRI treatment by investigating the effects of miR-190-5p and its downstream target on the structure and function of myocardial cells.

          Methods

          We injected agomir miR-190-5p into the tail vein of rats to increase the expression of miR-190-5p in rat myocardial cells and made an I/R rat model by coronary artery occlusion. We used 2,3,5-triphenyl tetrazolium chloride staining, lactate dehydrogenase (LDH) detection, echocardiography, and hematoxylin-eosin (HE) staining to determine the degree of myocardial injury in I/R rats. In addition, we detected the expression of inflammatory factors and apoptosis-related molecules in rat serum and myocardial tissue to determine the level of inflammation and apoptosis in rat myocardium. Finally, we determined the downstream target of miR-190-5p by Targetscan system and dual luciferase reporter assay.

          Results

          The expression of miR-190-5p in an I/R rat myocardium was significantly lower than that in normal rats. After treatment of I/R rats with agomir miR-190-5p, the ischemic area of rat myocardium and the concentration of LDH decreased. The results of echocardiography and HE staining also found that overexpression of miR-190-5p improved the structure and function of rat myocardium. miR-190-5p was also found to improve the viability of H9c2 cells in vitro and reduce the level of apoptosis of H9c2 cells. The results of Targetscan system and dual luciferase reporter assay found that miR-190-5p targeted to inhibit pleckstrin homology domain leucine-rich repeat protein phosphatase 1 (PHLPP1). In addition, inhibition of PHLPP1 was found to improve the viability of H9c2 cells.

          Conclusion

          Therefore, miR-190-5p can reduce the inflammation and apoptosis of myocardium by targeting PHLPP1, thereby alleviating MIRI.

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          Most cited references 22

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          Myocardial ischemia-reperfusion injury: a neglected therapeutic target.

          Acute myocardial infarction (MI) is a major cause of death and disability worldwide. In patients with MI, the treatment of choice for reducing acute myocardial ischemic injury and limiting MI size is timely and effective myocardial reperfusion using either thombolytic therapy or primary percutaneous coronary intervention (PPCI). However, the process of reperfusion can itself induce cardiomyocyte death, known as myocardial reperfusion injury, for which there is still no effective therapy. A number of new therapeutic strategies currently under investigation for preventing myocardial reperfusion injury have the potential to improve clinical outcomes in patients with acute MI treated with PPCI.
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            ROS and redox signaling in myocardial ischemia-reperfusion injury and cardioprotection.

            Ischemia-reperfusion (IR) injury is central to the pathology of major cardiovascular diseases, such as stroke and myocardial infarction. IR injury is mediated by several factors including the elevated production of reactive oxygen species (ROS), which occurs particularly at reperfusion. The mitochondrial respiratory chain and NADPH oxidases of the NOX family are major sources of ROS in cardiomyocytes. The first part of this review discusses recent findings and controversies on the mechanisms of superoxide production by the mitochondrial electron transport chain during IR injury, as well as the contribution of the NOX isoforms expressed in cardiomyocytes, NOX1, NOX2 and NOX4, to this damage. It then focuses on the effects of ROS on the opening of the mitochondrial permeability transition pore (mPTP), an inner membrane non-selective pore that causes irreversible damage to the heart. The second part analyzes the redox mechanisms of cardiomyocyte mitochondrial protection; specifically, the activation of the hypoxia-inducible factor (HIF) pathway and the antioxidant transcription factor Nrf2, which are both regulated by the cellular redox state. Redox mechanisms involved in ischemic preconditioning, one of the most effective ways of protecting the heart against IR injury, are also reviewed. Interestingly, several of these protective pathways converge on the inhibition of mPTP opening during reperfusion. Finally, the clinical and translational implications of these cardioprotective mechanisms are discussed.
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              • Article: not found

              A review of melatonin as a suitable antioxidant against myocardial ischemia-reperfusion injury and clinical heart diseases.

              Cardiac tissue loss is one of the most important factors leading to the unsatisfactory recovery even after treatment of ischemic heart disease. Melatonin, a circadian molecule with marked antioxidant properties, protects against ischemia-reperfusion (IR) injury. In particular, the myocardial protection of melatonin is substantial. We initially focus on the cardioprotective effects of melatonin in myocardial IR. These studies showed how melatonin preserves the microstructure of the cardiomyocyte and reduces myocardial IR injury. Thereafter, downstream signaling pathways of melatonin were summarized including Janus kinase 2/signal transducers and activators of transcription 3, nitric oxide-synthase, and nuclear factor erythroid 2 related factor 2. Herein, we propose the clinical applications of melatonin in several ischemic heart diseases. Collectively, the information summarized in this review (based on in vitro, animal, and human studies) should serve as a comprehensive reference for the action of melatonin in cardioprotection and hopefully will contribute to the design of future experimental research.
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                Author and article information

                Contributors
                Journal
                Dis Markers
                Dis Markers
                DM
                Disease Markers
                Hindawi
                0278-0240
                1875-8630
                2021
                25 November 2021
                : 2021
                Affiliations
                1Department of Cardiology, The Second Hospital of Jilin University, Changchun, China
                2Department of Cardiology, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
                Author notes

                Academic Editor: Francesco Busardò

                Article
                10.1155/2021/8709298
                8639278
                b279ec8c-f65c-4f38-a42d-6ae9bbbd5435
                Copyright © 2021 Yangxue Li et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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