mRNA-miRNA integrative analysis of diabetes-induced cardiomyopathy in rats

Lopes, Mariana Borges Sodré; Freitas, Renata Caroline Costa de; Hirata, Mário Hiroyuki; Hirata, Rosario D C; Rezende, Adriana Augusto de; Silbiger, Vivian N.; Bortolin, Raul Hernandes; Luchessi, André Ducati

doi:10.2741/s483

Cited by 15 publications

(2 citation statements)

References 6 publications

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“…In vascular disease, miR-21 knockout exacerbated AngII-induced TAAD formation in mice through the TGF-β pathway (Huang et al, 2018). Several studies have shown that miR-21 expression is upregulated in the ventricles under diabetic conditions (Guo and Nair, 2017;Lopes et al, 2017). In this study, we found that the expression level of miR-21 was upregulated in the heart tissue of diabetic mice and in H9c2 cells treated with high glucose, which was consistent with previous studies (Thum et al, 2008).…”

Section: Discussionsupporting

confidence: 91%

Vildagliptin Attenuates Myocardial Dysfunction and Restores Autophagy via miR-21/SPRY1/ERK in Diabetic Mice Heart

Meng

Han

et al. 2021

Front. Pharmacol.

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Aim: Vildagliptin (vild) improves diastolic dysfunction and is associated with a lower relative risk of major adverse cardiovascular events in younger patients. The present study aimed to evaluate whether vild prevents the development of diabetic cardiomyopathy in type 2 diabetic mice and identify its underlying mechanisms.Methods: Type 2 diabetic mouse model was generated using wild-type (WT) (C57BL/6J) and miR-21 knockout mice by treatment with HFD/STZ. Cardiomyocyte-specific miR-21 overexpression was achieved using adeno-associated virus 9. Echocardiography was used to evaluate cardiac function in mice. Morphology, autophagy, and proteins levels in related pathway were analyzed. qRT-PCR was used to detect miR-21. Rat cardiac myoblast cell line (H9c2) cells were transfected with miR-21 mimics and inhibitor to explore the related mechanisms of miR-21 in diabetic cardiomyopathy.Results: Vild restored autophagy and alleviated fibrosis, thereby enhancing cardiac function in DM mice. In addition, miR-21 levels were increased under high glucose conditions. miR-21 knockout DM mice with miR-21 knockout had reduced cardiac hypertrophy and cardiac dysfunction compared to WT DM mice. Overexpression of miR-21 aggravated fibrosis, reduced autophagy, and attenuated the protective effect of vild on cardiac function. In high-glucose-treated H9c2 cells, the downstream effectors of sprouty homolog 1 (SPRY1) including extracellular signal-regulated kinases (ERK) and mammalian target of rapamycin showed significant changes following transfection with miR-21 mimics or inhibitor.Conclusion: The results of our study indicate that vild prevents DCM by restoring autophagy through the miR-21/SPRY1/ERK/mTOR pathway. Therefore, miR-21 is a target in the development of DCM, and vild demonstrates significant potential for clinical application in prevention of DCM.

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Section: Discussionsupporting

confidence: 91%

Vildagliptin Attenuates Myocardial Dysfunction and Restores Autophagy via miR-21/SPRY1/ERK in Diabetic Mice Heart

Meng

Han

et al. 2021

Front. Pharmacol.

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“…The bioinformatics and proteomics analysis of recent evidence found that miR-29c expression in cardiomyocytes is inversely correlated with GLUT4 expression [74]. The expression of miR-17 was upregulated in diabetic cardiac myopathy [75]. We, therefore, speculated that GLUT4, KLF15, selenoproteins, and IGF-1 might be the key targets of specific miRNAs, including miR-223, miR-133, miR-223-3p, miR-200a-5p, miR-1, miR-133a, miR-133b, miR-150, and may regulate the transport and uptake of glucose in cardiomyocytes.…”

Section: Mirna-regulated Glucose Metabolismmentioning

confidence: 99%

Cardiac Metabolism and MiRNA Interference

Sumaiya

Ponnusamy

Natarajaseenivasan

et al. 2022

IJMS

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The aberrant increase in cardio-metabolic diseases over the past couple of decades has drawn researchers’ attention to explore and unveil the novel mechanisms implicated in cardiometabolic diseases. Recent evidence disclosed that the derangement of cardiac energy substrate metabolism plays a predominant role in the development and progression of chronic cardiometabolic diseases. Hence, in-depth comprehension of the novel molecular mechanisms behind impaired cardiac metabolism-mediated diseases is crucial to expand treatment strategies. The complex and dynamic pathways of cardiac metabolism are systematically controlled by the novel executor, microRNAs (miRNAs). miRNAs regulate target gene expression by either mRNA degradation or translational repression through base pairing between miRNA and the target transcript, precisely at the 3’ seed sequence and conserved heptametrical sequence in the 5’ end, respectively. Multiple miRNAs are involved throughout every cardiac energy substrate metabolism and play a differential role based on the variety of target transcripts. Novel theoretical strategies have even entered the clinical phase for treating cardiometabolic diseases, but experimental evidence remains inadequate. In this review, we identify the potent miRNAs, their direct target transcripts, and discuss the remodeling of cardiac metabolism to cast light on further clinical studies and further the expansion of novel therapeutic strategies. This review is categorized into four sections which encompass (i) a review of the fundamental mechanism of cardiac metabolism, (ii) a divulgence of the regulatory role of specific miRNAs on cardiac metabolic pathways, (iii) an understanding of the association between miRNA and impaired cardiac metabolism, and (iv) summary of available miRNA targeting therapeutic approaches.

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