MicroRNA‑138 attenuates myocardial ischemia reperfusion injury through inhibiting mitochondria‑mediated apoptosis by targeting HIF1‑α

Liu, Yan; Zou, Jiwen; Liu, Xiaoyan; Zhang, Quan

doi:10.3892/etm.2019.7976

Cited by 23 publications

(23 citation statements)

References 40 publications

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“…miR-138 serves an anti-apoptotic role by directly affecting the expression levels of caspase and Bcl-2 family members, as well as activation of c-Jun N-terminal kinase and p38 MAPK signaling ( 9 , 24 , 25 ). Furthermore, miR-138 has been found to exert anti-inflammatory effects by regulating the AKT and NF-κB signaling pathways ( 26 , 27 ), and to maintain mitochondrial homeostasis by targeting hypoxia-inducible factor 1-α ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Hyperoside protects cardiomyocytes against hypoxia‑induced injury via upregulation of microRNA‑138

He¹,

Yin²,

Wu³

et al. 2021

Mol Med Rep

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Following hypoxia, cardiomyocytes are susceptible to damage, against which microRNA (miR)-138 may act protectively. Hyperoside (Hyp) is a Chinese herbal medicine with multiple biological functions that serve an important role in cardiovascular disease. The aim of the present study was to investigate the role of Hyp in hypoxic cardiomyocytes and its effect on miR-138. A hypoxia model was established in both H9C2 cells and C57BL/6 mice, which were stimulated by Hyp. The expression levels of miR-138 were increased in the hypoxic myocardium in the presence of Hyp at concentrations of >50 µmol/l in vivo and >50 mg/kg in vitro . Using Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine assays, it was observed that Hyp improved hypoxia-induced impairment of cell proliferation. Cell apoptosis was evaluated by flow cytometry and a TUNEL assay. The number of apoptotic cells in the Hyp group was lower than that in the control group. As markers of myocardial injury, the levels of lactate dehydrogenase, creatine kinase-myocardial band isoenzyme and malondialdehyde were decreased in the Hyp group compared with the control group, whereas the levels of superoxide dismutase were increased. A marked decrease in the levels of cleaved caspase-3 and cleaved poly(ADP) ribose polymerase and a marked increase in expression levels of Bcl-2 were observed in the presence of Hyp. However, miR-138 inhibition by antagomir attenuated the protective effects of Hyp. Furthermore, Hyp treatment was associated with marked downregulation of mixed lineage kinase 3 and lipocalin-2, but not pyruvate dehydrogenase kinase 1, in hypoxic H9C2 cells. These findings demonstrated that Hyp may be beneficial for myocardial cell survival and may alleviate hypoxic injury via upregulation of miR-138, thereby representing a promising potential strategy for clinical cardioprotection.

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Section: Discussionmentioning

confidence: 99%

Hyperoside protects cardiomyocytes against hypoxia‑induced injury via upregulation of microRNA‑138

He¹,

Yin²,

Wu³

et al. 2021

Mol Med Rep

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“…In vivo experiments have demonstrated that overexpression of miR-335 enhances the transcriptional activity of HIF-1α, increases the expression levels of HO-1 and iNOS and inhibits the opening of mitochondrial PTP, thereby decreasing myocardial infarct size and myocardial apoptosis as well as improving MIRI ( 41 ). Liu et al ( 60 ) demonstrated that sirtuin 1 (SIRT1) also acts as a transcriptional repressor to suppress the expression levels of miR-138 in adult sensory neurons in response to peripheral nerve injury. Therefore, miR-138 and SIRT1 can form a mutual negative feedback regulatory loop, which provides a novel mechanism for controlling intrinsic axon regeneration.…”

Section: Roles Of Hif-1α In Mirimentioning

confidence: 99%

“…The overexpression of miRNA-138 can decrease apoptosis following myocardial IR by decreasing the expression levels of HIF-1α. This may be explained by the difference between early and prolonged hypoxia ( 60 ). During early hypoxia, changes in miRNA levels may contribute to the accumulation of HIF-1α and maintain the steady-state levels of HIF-2 and HIF-3 ( 61 ).…”

Section: Roles Of Hif-1α In Mirimentioning

confidence: 99%

HIF‑1α in myocardial ischemia‑reperfusion injury (Review)

et al. 2021

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Myocardial ischemia-reperfusion injury (MIRI) is a severe injury to the ischemic myocardium following the recovery of blood flow. Currently, there is no effective treatment for MIRI in clinical practice. Over the past two decades, biological studies of hypoxia and hypoxia-inducible factor-1α (HIF-1α) have notably improved understanding of oxygen homeostasis. HIF-1α is an oxygen-sensitive transcription factor that mediates adaptive metabolic responses to hypoxia and serves a pivotal role in MIRI. In particular, previous studies have demonstrated that HIF-1α improves mitochondrial function, decreases cellular oxidative stress, activates cardioprotective signaling pathways and downstream protective genes and interacts with non-coding RNAs. The present review summarizes the roles and associated mechanisms of action of HIF-1α in MIRI. In addition, HIF-1α-associated MIRI intervention, including natural compounds, exosomes, ischemic preconditioning and ischemic post-processing are presented. The present review provides evidence for the roles of HIF-1α activation in MIRI and supports its use as a therapeutic target. Contents 1. Introduction 2. Molecular characteristics of HIF-1α 3. HIF-1α-mediated transcriptional responses to hypoxia 4. Roles of HIF-1α in MIRI 5. Involvement of HIF-1α in the myocardial protective effects of natural compounds against MIRI 6. Roles of HIF-1α in myocardial ischemic pre-and post-conditioning 7. Future perspectives

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“…MicroRNAs (miRNAs) are short non‐coding RNAs with length of 19–24 nt, which bind to the 3′‐untranslated regions (3′UTR) of target mRNAs to modulate the translation into protein or promote the decay of expressed transcripts 8 . Several particular miRNAs including miR‐374 9 and miR‐138 10 were involved in the progression of MIRI. As one of the miRNAs, the role of miR‐19a‐3p has been discussed in myocardial ischemia, 11 myocardial hypertrophy 12 and fibrogenesis in human cardiac fibroblasts 13 .…”

Section: Introductionmentioning

confidence: 99%

Inhibited histone deacetylase 3 ameliorates myocardial ischemia–reperfusion injury in a rat model by elevating microRNA‐19a‐3p and reducing cyclin‐dependent kinase 2

Song

Li²,

Quan

et al. 2020

IUBMB Life

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ObjectiveOver the years, the roles of microRNAs (miRNAs) and histone deacetylase 3 (HDAC3) in human diseases have been investigated. This study focused on the effect of miR‐19a‐3p and HDAC3 in myocardial ischemia–reperfusion (I/R) injury (MIRI) by targeting cyclin‐dependent kinase 2 (CDK2).MethodsThe I/R rat models were established by coronary artery ligation, which were then treated with RGFP966 (an inhibitor of HDAC3), miR‐19a‐3p agomir or antagomir, or silenced CDK2 to explore their roles in the cardiac function, pathological changes of myocardial tissues, myocardial infarction area, inflammatory factors and oxidative stress factors in rats with MIRI. The expression of miR‐19a‐3p, HDAC3, and CDK2 was determined by RT‐qPCR and western blot assay, and the interaction among which was also verified by online prediction, luciferase activity assay and ChIP assay.ResultsThe results indicated that HDAC3 and CDK2 were upregulated while miR‐19a‐3p was downregulated in myocardial tissues of I/R rats. The inhibited HDAC3/CDK2 or elevated miR‐19a‐3p could promote cardiac function, attenuate pathological changes, inflammatory reaction, oxidative stress, myocardial infarction area and apoptosis of myocardial tissues. HDAC3 mediates miR‐19a‐3p and CDK2 is targeted by miR‐19a‐3p.ConclusionInhibited HDAC3 ameliorates MIRI in a rat model by elevating miR‐19a‐3p and reducing CDK2, which may contribute to the treatment of MIRI.

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MicroRNA‑138 attenuates myocardial ischemia reperfusion injury through inhibiting mitochondria‑mediated apoptosis by targeting HIF1‑α

Cited by 23 publications

References 40 publications

Hyperoside protects cardiomyocytes against hypoxia‑induced injury via upregulation of microRNA‑138

Hyperoside protects cardiomyocytes against hypoxia‑induced injury via upregulation of microRNA‑138

HIF‑1α in myocardial ischemia‑reperfusion injury (Review)

Inhibited histone deacetylase 3 ameliorates myocardial ischemia–reperfusion injury in a rat model by elevating microRNA‐19a‐3p and reducing cyclin‐dependent kinase 2

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