MicroRNA-486-5p targeting PTEN Protects Against Coronary Microembolization-Induced Cardiomyocyte Apoptosis in Rats by activating the PI3K/AKT pathway

Zhu, Han-Hua; Wang, Xiantao; Sun, Yani; He, Wei; Liang, Jing; Mo, Bing-hai; Li, Lang

doi:10.1016/j.ejphar.2019.03.045

Cited by 42 publications

(34 citation statements)

References 29 publications

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“…13 miR-486-5p has been reported to suppress cardiomyocyte apoptosis and improve cardiac function though activation of PI3K/Akt pathway in rats. 14 Compared to the wild-type mice, double deletion of miR-133a-1 and miR-133a-2 mice show a 2.5-fold increase in cardiomyocyte proliferation 15 in hearts with an elevated expression of α-smooth muscle actin (α-SMA), 15 which is critical for fibroblasts differentiation to myofibroblasts. 16 miR-185-5p dramatically expresses lower in hearts from mice following MI than that from normal mice, and miR-185-5p has been confirmed to inhibit cell proliferations, migrations and tube formations at cellular level.…”

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confidence: 99%

MiR‐590‐3p regulates proliferation, migration and collagen synthesis of cardiac fibroblast by targeting ZEB1

Yuan

Pan

Wen

et al. 2019

J Cellular Molecular Medi

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Previous studies have implicated the attractive and promising role of miR‐590‐3p to restore the cardiac function following myocardial infarction (MI). However, the molecular mechanisms for how miR‐590‐3p involves in cardiac fibrosis remain largely unexplored. Using human cardiac fibroblasts (HCFs) as the cellular model, luciferase report assay, mutation, EdU assay and transwell migration assay were applied to investigate the biological effects of miR‐590‐3p on the proliferation, differentiation, migration and collagen synthesis of cardiac fibroblasts. We found that miR‐590‐3p significantly suppressed cell proliferation and migration of HCFs. The mRNA and protein expression levels of α‐SMA, Col1A1 and Col3A were significantly decreased by miR‐590‐3p. Moreover, miR‐590‐3p directly targeted at the 3’UTR of ZEB1 to repress the translation of ZEB1. Interfering with the expression of ZEB1 significantly decreased the cell proliferation, migration activity, mRNA and protein expressions of α‐SMA, Col1A1 and Col3A. Furthermore, the expressions of miR‐590‐3p and ZEB1 were identified in infarct area of MI model in pigs. Collectively, miR‐590‐3p suppresses the cell proliferation, differentiation, migration and collagen synthesis of cardiac fibroblasts by targeting ZEB1. These works will provide useful biological information for future studies on potential roles of miR‐590‐3p as the therapeutic target to recover cardiac function following MI.

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mentioning

confidence: 99%

MiR‐590‐3p regulates proliferation, migration and collagen synthesis of cardiac fibroblast by targeting ZEB1

Yuan

Pan

Wen

et al. 2019

J Cellular Molecular Medi

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“…Unlike proximal epicardial coronary artery occlusion, CME causes myocardial microinfarction, but its effect on the degree of LV systolic dysfunction does not correlate with the magnitude of cardiomyocyte necrosis 22‐24 . Cardiac cell apoptosis around microvascular infarction plays a key role in the progressive deterioration of cardiac function caused by myocardial injury after CME, and inhibiting apoptosis can ameliorate CME‐induced myocardial injury 9,25,26 . In this study, the rats subjected to CME showed elevated levels of myocardial injury markers, cardiac dysfunction, microinfarction, and increased cardiomyocyte apoptosis, consistent with the diverse pathophysiological manifestations of CME.…”

Section: Discussionmentioning

confidence: 51%

Nicorandil inhibits cardiomyocyte apoptosis and improves cardiac function by suppressing the HtrA2/XIAP/PARP signaling after coronary microembolization in rats

Zheng

Long

Qin

et al. 2021

Pharmacology Res & Perspec

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Cardiomyocyte apoptosis is a key factor in the deterioration of cardiac function after coronary microembolization (CME). Nicorandil (NIC) affects myocardial injury, which may be related to the inhibition of apoptosis. However, the specific mechanism of cardioprotection has not been elucidated. Therefore, we analyzed the impact of NIC on cardiac function in rats subjected to CME and its effect on the high‐temperature requirement peptidase 2/X‐linked inhibitor of apoptosis protein/poly ADP‐ribose polymerase (HtrA2/XIAP/PARP) pathway. Sprague Dawley rats were divided into four groups: Sham, CME, CME + NIC, and CME + UCF. Echocardiography was performed 9 hours after CME. Myocardial injury markers were evaluated in blood samples, and the heart tissue was collected for hematoxylin‐eosin staining, hematoxylin basic fuchsin picric acid staining staining, TdT‐mediated DUTP nick end labeling (TUNEL) staining, Western blot analysis of the HtrA2/XIAP/PARP pathway, and transmission electron microscopy. NIC ameliorated cardiac dysfunctioncaused by CME and reduced serum levels of CK‐MB and LDH. In addition, NIC decreased myocardial microinfarct size and apoptotic index. NIC reduced the Bax/Bcl‐2 ratio, levels of cleaved caspase 3/9, cytoplasmic HtrA2, and cleaved PARP, and increased the level of XIAP. The effects of NIC were similar to those of the HtrA2 inhibitor, UCF101. This study demonstrated that NIC reduces CME‐induced myocardial injury, reduces mitochondrial damage, and improves myocardial function. The reduction in cardiomyocyte apoptosis by NIC may be mediated by the HtrA2/XIAP/PARP signaling pathway.

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“…Moreover, miR-214 was further proved to be a regulator of DPP4 in the adipocytes. Accumulated evidence demonstrate that miRNAs could exist pivotal regulatory effects in the pathogenesis of various diseases mediated by the target genes [24][25][26][27]. In the disease progression of IR, some members of miRNAs with critical roles have also been reported [28].…”

Section: Discussionmentioning

confidence: 99%

Aberrant expression of miR-214 is associated with obesity-induced insulin resistance as a biomarker and therapeutic

Cheng

Yuan

et al. 2020

Diagn Pathol

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Background: Insulin resistance (IR) in obesity is associated with the occurrence of metabolic and cardiovascular diseases. Dipepidyl peptidase 4 (DPP4) plays a pivotal role during the development of IR, and was found to be a target gene of microRNA-214 (miR-214) in our study. This study sought to assess the expression and clinical value of miR-214 in obese patients with IR, and investigate its therapeutic potential in obese rats and adipocytes with IR. Methods: Serum expression of miR-214 in obese patients with or without IR was estimated by quantitative realtime-PCR. A receiver operating characteristic curve was plotted to evaluate the diagnostic value of miR-214 in the patients. Obesity-induced IR animal and cell models were constructed, and the therapeutic ability of miR-214 was explored. Results: Serum expression of miR-214 was decreased in obese patients compared with the healthy controls, and the lowest expression was observed in the cases with IR. Downregulation of miR-214 was significantly correlated with the serum DPP4 levels and HOMA-IR of the patients upon IR conditions, and was demonstrated to perform diagnostic accuracy for distinguishing obese patients with IR from those without IR. In obesity-associated IR animal and cell models, the downregulation of miR-214 was also been detected. According to the measurement of glucose and insulin tolerance and glucose uptake abilities, we found that the overexpression of miR-214 could be used to alleviate IR in the IR models, especially when collaboratively used with DPP4 inhibitor vildagliptin. Conclusion: All data revealed that miR-214, as a regulator of DPP4, is decreased in obese patients with IR and may serve as a diagnostic biomarker. The upregulation of miR-214 could improve IR in obese rats and adipocytes, indicating that miR-214 has the therapeutic potential for obesity and IR.

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MicroRNA-486-5p targeting PTEN Protects Against Coronary Microembolization-Induced Cardiomyocyte Apoptosis in Rats by activating the PI3K/AKT pathway

Cited by 42 publications

References 29 publications

MiR‐590‐3p regulates proliferation, migration and collagen synthesis of cardiac fibroblast by targeting ZEB1

MiR‐590‐3p regulates proliferation, migration and collagen synthesis of cardiac fibroblast by targeting ZEB1

Nicorandil inhibits cardiomyocyte apoptosis and improves cardiac function by suppressing the HtrA2/XIAP/PARP signaling after coronary microembolization in rats

Aberrant expression of miR-214 is associated with obesity-induced insulin resistance as a biomarker and therapeutic

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