miR-217 Promotes Cardiac Hypertrophy and Dysfunction by Targeting PTEN

Nie, Xiang; Fan, Jiahui; Li, Huaping; Yin, Zongsheng; Zhang, Yanru; Dai, Bingbing; Dong, Nianguo; Chen, Chen; Wang, Dao Wen

doi:10.1016/j.omtn.2018.05.013

Cited by 110 publications

(85 citation statements)

References 54 publications

(65 reference statements)

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“…miR-378 in exosomes, which is secreted from cardiomyocytes, inhibited excessive cardiac fibrosis [19]. Further, miR-217 in exosomes, which is secreted from cardiomyocytes, promoted cardiac fibrosis processes, cardiac hypertrophy, and cardiac fibrosis processes [20]. However, the effects of miRNA in EPC-derived exosomes on MEndoT and myocardial fibrosis remain unknown.…”

Section: Introductionmentioning

confidence: 99%

YBX-1 mediated sorting of miR-133 into hypoxia/reoxygenation-induced EPC-derived exosomes to increase fibroblast angiogenesis and MEndoT

et al. 2019

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Background: Myocardial fibrosis is a common pathophysiological change in cardiovascular disease, which can cause cardiac dysfunction and even sudden death. Excessively activated fibroblasts proliferate and secret excessive extracellular matrix (ECM) components, resulting in normal cardiac structural damage and cardiac fibrosis. We previously found that human endothelial progenitor cell (EPC)-derived exosomes, after hypoxia/reoxygenation (H/R) induction, could significantly increase the mesenchymal-endothelial transition (MEndoT) compared to normal culture EPC-derived exosomes. Exosomes have been shown to carry different nucleic acids, including microRNAs. However, the effects of microRNAs in EPC-derived exosomes on MEndoT and myocardial fibrosis remain unknown. Methods: EPCs were isolated from human peripheral blood, and fibroblasts were isolated from rat hearts, then transfected with miR-133 inhibitor, si-YBX-1, and ov-YBX-1 into EPCs. After H/R induction for 48 h, isolation and characterization of exosomes derived from human EPCs were performed. Finally, fibroblasts were treated by exosome at 48 h. The expression of miR-133 was measured by qRT-PCR; YBX-1 expression was measured by qRT-PCR and western blot. Angiopoiesis was measured by tube formation assay. Endothelial markers and fibrosis markers were measured by western blot. Results: H/R treatment promoted miR-133 expression in EPCs and EPC-derived exosomes. miR-133 could be incorporated into exosomes and transmitted to cardiac fibroblasts, increasing the angiogenesis and MEndoT of cardiac fibroblasts. miR-133 silencing in H/R-induced EPCs could inhibit miR-133 expression in EPCs and EPCsderived exosomes. miR-133 silencing in H/R-induced EPCs could inhibit the angiogenesis and MEndoT of cardiac fibroblasts and reverse the effect of H/R treatment. Additionally, miR-133 was specially sorted into H/R-induced EPCderived exosomes via YBX-1. YBX-1 silencing inhibited miR-133 transfer and reduced fibroblast angiogenesis and MEndoT. Conclusion: miR-133 was specially sorted into H/R-induced EPC-derived exosomes via YBX-1 to increase fibroblast angiogenesis and MEndoT.

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Section: Introductionmentioning

confidence: 99%

YBX-1 mediated sorting of miR-133 into hypoxia/reoxygenation-induced EPC-derived exosomes to increase fibroblast angiogenesis and MEndoT

et al. 2019

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“…Notably, PTEN, also known as mutated in multiple advanced cancers 1 (MMAC1), is involved in numerous cellular signalling pathways, including the phosphatidylinositol‐3‐kinase (PI3K)/AKT/mTOR pathway . As mentioned in prior studies, shortage of PTEN in myocardial tissue leads to activation of the AKT/mTOR pathway, which ultimately enhances pathological cardiac hypertrophy . Moreover, bioinformatics analysis has predicted that PTEN is one of the target genes of miR‐29a.…”

Section: Introductionmentioning

confidence: 99%

miR‐29a promotes pathological cardiac hypertrophy by targeting the PTEN/AKT/mTOR signalling pathway and suppressing autophagy

Shi

Chu

et al. 2019

Acta Physiologica

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Aim: Although miR-29 has emerged as a crucial non-coding RNA in the regulation of pathological cardiac hypertrophy, further exploration of its specific mechanisms is necessary to resolve controversy about its major role in this condition. This study therefore evaluated the role of miR-29a and whether it acts through the PTEN/AKT/ mTOR pathway. Methods: In this study, a rat model of pressure-induced cardiac hypertrophy was established by transverse aortic constriction and verified by echocardiography, histological analysis and quantitative RT-PCR. At the cellular level, we explored the role of miR-29a in angiotensin II-stimulated hypertrophic H9c2 cardiomyoblasts by transfecting the cells with miR-29a inhibitor and mimic. The relationship between miR-29a and the signalling pathway was investigated with dual luciferase reporter assays, immunofluorescence analysis and Western blotting. We also examined whether autophagy is involved in the regulatory mechanism of miR-29a through transmission electron microscopy and detection of autophagy-associated proteins. Results:The results showed that miR-29a was upregulated both in rats 4 weeks after surgery and in 10 −6 M angiotensin II-stimulated cells. In contrast, inhibition of miR-29a partially attenuated angiotensin II-induced hypertrophy. Additionally, bioinformatics analysis revealed that PTEN was one of the target genes of miR-29a, which was also verified by luciferase assay. The results of immunofluorescence and Western blotting indicated that overexpression of miR-29a inhibited the expression of PTEN, activated the AKT/mTOR pathway and suppressed autophagy, which ultimately led to cardiac hypertrophy. Conclusion: In pathological cardiac hypertrophy, miR-29a was overexpressed and promoted cardiac hypertrophy by regulating the PTEN/AKT/mTOR pathway and suppressing autophagy. K E Y W O R D Sautophagy, microRNA-29a, pathological cardiac hypertrophy, PTEN/AKT/mTOR 2 of 12 | SHI et al.How to cite this article: Shi J-Y, Chen C, Xu X, Lu Q. miR-29a promotes pathological cardiac hypertrophy by targeting the PTEN/AKT/mTOR signalling pathway and suppressing autophagy. Acta Physiol.

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“…Considering that cardiomyocytes lose their ability to divide soon after birth, cardiac hypertrophy is an important adaptive response to maintain or increase the cardiac output of the organism (19). We observed that miR-378a-3p, miR-100-5p and miR-486-5p are involved in the regulation of several molecules related to activation pathways that lead to a hypertrophic response at the cellular level.…”

Section: Discussionmentioning

confidence: 94%

Gene networks and canonical pathways associated with a favorable blood pressure response after CPAP treatment: the HIPARCO score post hoc analysis

Zapater

Santamaria-Martos

Targa

et al. 2020

Preprint

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Background: Several studies report an association between microRNAs (miRNAs) and hypertension or cardiovascular disease. In a previous study, we observed a cluster of three miRNAs (miR-378a-3p, miR-100-5p, and miR-486-5p) functionally associated with the cardiovascular system that predicted a favorable blood pressure response to continuous positive airway pressure (CPAP) treatment in patients with resistant hypertension (RH) and obstructive sleep apnea (OSA) (HIPARCO score). However, little is known regarding the molecular mechanisms underlying this. Thus, the aim of the present study was to perform a post hoc analysis to investigate the genes, functions and pathways related to the previously found HIPARCO-score miRNAs. Methods: We performed an enrichment analysis using Ingenuity Pathway Analysis. The genes potentially associated with the miRNAs were filtered based on their confidence level. Particularly for cardiovascular disease, only the genes regulated by at least two of the miRNAs were studied. Results: We observed that the miRNAs studied regulate 200-249 molecules associated with several functions and diseases, including extracranial solid tumors and abdominal neoplasms, among others. The cardiac hypertrophy and NF-kB signaling pathways were identified as the cardiovascular pathways most influenced by these three miRNAs. Conclusions: Considering this, the mechanisms by which CPAP treatment decreases the blood pressure in OSA patients with RH could be related to these pathways. Further investigations will be necessary to confirm these findings, contributing to the elucidation of new therapeutic targets in patients that do not respond to CPAP treatment.

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miR-217 Promotes Cardiac Hypertrophy and Dysfunction by Targeting PTEN

Cited by 110 publications

References 54 publications

YBX-1 mediated sorting of miR-133 into hypoxia/reoxygenation-induced EPC-derived exosomes to increase fibroblast angiogenesis and MEndoT

YBX-1 mediated sorting of miR-133 into hypoxia/reoxygenation-induced EPC-derived exosomes to increase fibroblast angiogenesis and MEndoT

miR‐29a promotes pathological cardiac hypertrophy by targeting the PTEN/AKT/mTOR signalling pathway and suppressing autophagy

Gene networks and canonical pathways associated with a favorable blood pressure response after CPAP treatment: the HIPARCO score post hoc analysis

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