Role of microRNA-124 in cardiomyocyte hypertrophy inducedby angiotensin II

Bao, Qinxue; Chen, L.; Li, J.; Zhao, Mingyue; Wu, Si-Pei; Wu, Wenchao; Liu, X.

doi:10.14715/cmb/2017.63.4.4

Cited by 29 publications

(19 citation statements)

References 26 publications

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“…In addition, miR-124 was shown downregulated in myogenic conversion of bone marrow derived mesenchymal stem cells and affect the expression of cardiac-specific markers [17]. Furthermore, miR-124 was elevated in AngII-induced hypertrophic cardiomyocytes and inhibition of miR-124 effectively suppressed myocardial hypertrophy [18]. However, the relationship between miR-124 function and myocardial infarction remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of MicroRNA-124 Reduces Cardiomyocyte Apoptosis Following Myocardial Infarction via Targeting STAT3

He¹,

Liu²,

Guo³

et al. 2018

Cell Physiol Biochem

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Background/Aims: MicroRNAs play an important role in regulating myocardial infarction (MI)-induced cardiac injury. MicroRNA-124 (miR-124) plays a vital role in regulating cellular proliferation, differentiation and apoptosis. Although the alteration of miR-124 was confirmed in peripheral blood of MI patients, little is known regarding the biological functions of miR-124 in cardiomyocytes. This study was designed to explore the role of miR-124 in MI and its underlying mechanisms. Methods: Real-time PCR was used to quantify the microRNAs levels. TUNEL and Flow cytometry were performed to measure cell apoptosis. Western blot analysis was employed to detect expression of Bcl-2, Bax, Caspase-3 and STAT3 proteins. Results: We revealed that miR-124 was significantly up-regulated in a mice model of MI and in neonatal rat ventricular myocytes (NRVMs) with H₂O₂ treatment. H₂O₂ treatment induced cardiomyocyte injury with reduced cell viability and enhanced apoptotic cell death, whereas silencing expression of miR-124 by AMO-124 (antisense inhibitor oligodeoxyribonucleotides) alleviated these deleterious changes. AMO-124 decreased the expression of Bax and cleaved-caspase-3 and upregulated the expression of Bcl-2 in H₂O₂-treated NRVMs. Besides, AMO-124 improved mitochondrial dysfunction of NRVMs induced by H₂O₂ treatment. Moreover, antagomir-124 markedly decreased the infarct area and apoptotic cardiomyocytes and improved cardiac function in MI mice. Furthermore, we identified STAT3 as a direct target of miR-124, and downregulation of miR-124 ameliorated the diminished levels of STAT3 and p-STAT3 (Tyr705) in response to H₂O₂ or MI. STAT3 inhibitor, stattic, was shown to attenuate the elevation of p-STAT3 in NRVMs with AMO-124 transfection. Inhibiting of STAT3 activity by stattic abrogated protective effects of AMO-124 on H₂O₂-induced cardiomyocytes apoptosis. Conclusion: Taken together, our data demonstrate that downregulation of miR-124 inhibits MI-induced apoptosis through upregulating STAT3, which suggests the therapeutic potential of miR-124 for myocardial infarction.

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Section: Discussionmentioning

confidence: 99%

Inhibition of MicroRNA-124 Reduces Cardiomyocyte Apoptosis Following Myocardial Infarction via Targeting STAT3

He¹,

Liu²,

Guo³

et al. 2018

Cell Physiol Biochem

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“…It was reported previously that miR-124 aggravated the hypertrophic response of cardiomyocytes to Ang II, probably by increasing endoplasmic reticulum stress in vitro [ 31 ]. miR-124 was reported to inhibit the transdifferentiation from bone marrow-derived mesenchymal stem cells into cardiomyocytes in heart repair after injury by targeting STAT3 [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

MiR-124 aggravates failing hearts by suppressing CD151-facilitated angiogenesis in heart

et al. 2018

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Heart failure (HF) is the final common pathway of various cardiovascular diseases. Although it is well documented that reduction of cardiac angiogenesis contributes to the progression from adaptive cardiac hypertrophy to HF, the molecular mechanisms remain unknown. In the present study, we found that cardiac expression of miR-124 was increased in patients and mice with HF. Recombinant adeno-associated virus (rAAV)-mediated miR-124 over-expression aggravated angiotensin II (Ang II) infusion-induced cardiac dysfunction and abnormal cardiac angiogenesis in mice. In vitro, transfection of miR-124 mimics significantly promoted apoptosis and reduced viability, migration, tube formation, and nitric oxide release in endothelial cells. In addition, CD151 was identified as a direct target of miR-124. Endothelial cell injury caused by CD151 silencing was mimicked by miR-124 over-expression. Re-expression of CD151 attenuated miR-124-mediated suppression of cardiac angiogenesis and cardiac dysfunction in Ang II-treated mice. Our observations suggest that miR-124 is an important negative regulator of cardiac angiogenesis and cardiac function, likely by suppressing the expression of CD151 in heart cells. Modulation of miR-124 levels may provide new strategies and targets for HF therapy.

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“…This event consequently enhances β -MHC expression and further aggravates cardiac hypertrophy [28]. MiR-124 effectively represses AngII-induced neonatal cardiomyocytes hypertrophy by blocking the expression of calreticulin (CRT) and glucose-regulated protein (Grp78), an endoplasmic reticulum (ER) stress marker [29]. Several miRNAs reduce the expression of antihypertrophic factors and indirectly contribute to elevation of pathological hypertrophy.…”

Section: Mirna and Cardiac Hypertrophymentioning

confidence: 99%

MicroRNA as a Therapeutic Target in Cardiac Remodeling

Chen

Ponnusamy

Liu

et al. 2017

BioMed Research International

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MicroRNAs (miRNAs) are small RNA molecules that contain 18–25 nucleotides. The alterations in their expression level play crucial role in the development of many disorders including heart diseases. Myocardial remodeling is the final pathological consequence of a variety of myocardial diseases. miRNAs have central role in regulating pathogenesis of myocardial remodeling by modulating cardiac hypertrophy, cardiomyocytes injury, cardiac fibrosis, angiogenesis, and inflammatory response through multiple mechanisms. The balancing and tight regulation of different miRNAs is a key to drive the cellular events towards functional recovery and any fall in this leads to detrimental effect on cardiac function following various insults. In this review, we discuss the impact of alterations of miRNAs expression on cardiac hypertrophy, cardiomyocytes injury, cardiac fibrosis, angiogenesis, and inflammatory response. We have also described the targets (receptors, signaling molecules, transcription factors, etc.) of miRNAs on which they act to promote or attenuate cardiac remodeling processes in different type cells of cardiac tissues.

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Role of microRNA-124 in cardiomyocyte hypertrophy inducedby angiotensin II

Cited by 29 publications

References 26 publications

Inhibition of MicroRNA-124 Reduces Cardiomyocyte Apoptosis Following Myocardial Infarction via Targeting STAT3

Inhibition of MicroRNA-124 Reduces Cardiomyocyte Apoptosis Following Myocardial Infarction via Targeting STAT3

MiR-124 aggravates failing hearts by suppressing CD151-facilitated angiogenesis in heart

MicroRNA as a Therapeutic Target in Cardiac Remodeling

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