Transcoronary gradient of plasma microRNA 423-5p in heart failure: evidence of altered myocardial expression

Goldraich, Lívia Adams; Martinelli, Nidiane Carla; Matte, Úrsula; Cohen, Carolina Rodrigues; Andrades, Michael Éverton; Pimentel, Maurício; Biolo, Andréia; Clausell, Nadine Oliveira; Rohde, Luís Eduardo Paim

doi:10.3109/1354750x.2013.870605

Cited by 45 publications

(59 citation statements)

References 27 publications

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“…Besides these roles, miR-26a is also generally thought to be a tumor suppressor (Chen et al ., 2011; Reuland et al ., 2012; Salvatori et al ., 2012; Yang et al ., 2013). The expression of circulating miR-423 is related to myocardial function (Goldraich et al ., 2014). Here, we showed that arsenic exposure significantly down-regulated the expression of miR-423 in rat liver tissue.…”

Section: Discussionmentioning

confidence: 99%

Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

Ren

Gaile

Gong

et al. 2015

Toxicology and Applied Pharmacology

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Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100 mg/L) for 60 days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenic exposure and cluster membership (P-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate-cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g. miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

Ren

Gaile

Gong

et al. 2015

Toxicology and Applied Pharmacology

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“…A miR-score, based on cumulative levels of four miRs (including miR-423-5p), was able to discriminate HF patients and controls with an overall accuracy of 90% [42]. We have recently demonstrated a significant difference in miR-423-5p transcoronary gradient in HF outpatients compared with controls [11]. In the present study, we found a higher expression of miR-423-5p in HF patients, with no significant influence of obesity, reinforcing the concept that this particular miR is a reliable biomarker of HF.…”

Section: Accepted Manuscriptmentioning

confidence: 90%

“…Our group has previously demonstrated that levels of miR-423-5p are elevated in the coronary sinus of HF patients, suggesting that it has a A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 5 cardiac origin [11]. Other miRs, such as miR-21 and miR-221, have also been implicated in ventricular hypertrophy and HF pathogenesis [12,13].…”

Section: Introductionmentioning

confidence: 96%

Circulating microRNAs in obese and lean heart failure patients: A case–control study with computational target prediction analysis

Thome

Recamonde‐Mendoza

Cheuiche

et al. 2015

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Aims: MicroRNAs (miRs) regulate processes involved in both cardiac remodeling and obesity. We investigated if the expression of selected miRs in patients with heart failure (HF) is influenced by the presence of obesity. Methods:In this case-control study, we compared plasma levels of miR-21, -130b, -221, -423-5p, and the -221/-130b ratio in 57 age-and gender-matched subjects: 40 HF patients (20 obese HF and 20 lean HF) and 17 lean healthy controls. Body composition was estimated by bioelectrical impedance analysis. MiRs were measured by quantitative reverse transcription-PCR. Bioinformatics analysis was performed based on miRs findings to predict their putative targets and investigate their biological function.Results: HF was associated with increased miR-423-5p levels in both lean and obese patients (P<0.05 vs. controls) without differences between HF groups. MiR-130b levels were reduced in obese HF patients compared with HF lean (P=0.036) and controls (P=0.025). MiR-221 levels were non-significantly increased in obese HF patients. MiR-21 levels were not different among the groups. MiR-221/-130b ratio was increased in obese HF patients, and was positively associated with body fat percentage (r=0.43; P=0.002), body mass index (r=0.44; P=0.002), and waist circumference (r=0.40; P=0.020). Computational prediction of target genes followed by functional enrichment analysis indicated a relevant role of miR-130b and miR-221 in modulating the expression of genes associated to cardiovascular and endocrine diseases, and suggested their influence in important signaling mechanisms and in numerous processes related to the circulatory and endocrine systems. Conclusions:In HF patients, the presence of obesity is associated with a differential expression of selected miRs and the miR-221/-130b ratio had significant correlations with adiposity parameters. Computational target prediction analysis identified several interrelated pathways targeted by miR-130b and miR-221 with a known relationship with endocrine and cardiovascular diseases, representing potential mechanisms to be further validated.

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“…Thus, this evidence links the known neovascularization defects of diabetes mellitus to cardiac cells by means of miR-bearing exosomes. Another recent study of miRbased trans-coronary biomarkers identified miR-423-5p as a cardiacspecific heart failure plasma marker, positively correlating with the btype natriuretic peptide [185]. Interestingly, miR-423-5p has also been reported, in combination with miR-499, as a putative biomarker discriminating congestive heart failure from AMI [186].…”

Section: Circ-mirs: Biomarkers And/or Effectors In the Context Of Carmentioning

confidence: 94%

The mesmiRizing complexity of microRNAs for striated muscle tissue engineering

Quattrocelli

Sampaolesi

2015

Advanced Drug Delivery Reviews

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microRNAs (miRs) are small non-protein-coding RNAs, able to post-transcriptionally regulate many genes and exert pleiotropic effects. Alteration of miR levels in tissues and in the circulation has been associated with various pathological and regenerative conditions. In this regard, tissue engineering of cardiac and skeletal muscles is a fascinating context for harnessing the complexity of miR-based circuitries and signals. In this review, we will focus on miR-driven regulation of cardiac and skeletal myogenic routes in homeostatic and challenging states. Furthermore, we will survey the intriguing perspective of exosomal and circulating miRs as novel paracrine players, potentially useful for current and future approaches of regenerative medicine for the striated muscles.

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Transcoronary gradient of plasma microRNA 423-5p in heart failure: evidence of altered myocardial expression

Abstract: The difference in transcoronary gradients between HF outpatients and controls suggests that miR-423-5p has a cardiac origin. The positive correlation between miR-423-5p and BNP transcoronary gradients supports this hypothesis.

Cited by 45 publications

References 27 publications

Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

Circulating microRNAs in obese and lean heart failure patients: A case–control study with computational target prediction analysis

The mesmiRizing complexity of microRNAs for striated muscle tissue engineering

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