The prognostic value of circulating microRNAs in heart failure

Çakmak, Hüseyin Altuğ; Çoşkunpınar, Ender; İkitimur, Barış; Barman, Hasan Ali; Karadağ, Bilgehan; Tiryakioglu, Necip Ozan; Kahraman, Kadriye; Vural, Vural Ali

doi:10.2459/jcm.0000000000000233

Cited by 91 publications

(46 citation statements)

References 26 publications

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“…In male fetuses, 56 miRNAs were differentially expressed with IUGR (p<0.05, Figure 4), 12 of them were upregulated and 44 downregulated. Overall, 26 miRNAs were mapped to human; fourteen of them ( hsa-miR-1, -26a, -27b, -28, - 30e, -98, -99b, -143, -148a, -181a, -208b, -299-3p, -378, and -483 ) were previously linked to CVD [53, 61-72]. Only three of differentially expressed miRNAs - hsa-miR-1, -378, and -143 - were common for male and female IUGR fetuses and showed a significant reduction with IUGR vs. control.…”

Section: Resultsmentioning

confidence: 99%

Sexual dimorphism in the fetal cardiac response to maternal nutrient restriction

Muralimanoharan

Nakayasu

et al. 2017

Journal of Molecular and Cellular Cardiology

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Poor maternal nutrition causes intrauterine growth restriction (IUGR); however, its effects on fetal cardiac development are unclear. We have developed a baboon model of moderate maternal undernutrition, leading to IUGR. We hypothesized that IUGR affects fetal cardiac structure and metabolism. Six control pregnant baboons ate ad-libitum (CTRL)) or 70% CTRL from 0.16 of gestation (G). Fetuses were euthanized at C-section at 0.9G under general anesthesia. Male but not female IUGR fetuses showed left ventricular fibrosis inversely correlated with birth weight. Expression of extracellular matrix protein TSP-1 was increased (p<0.05) in male IUGR s. Expression of cardiac fibrotic markers TGFβ, SMAD3 and ALK-1 were downregulated in male IUGRs with no difference in females. Autophagy was present in male IUGR evidenced by upregulation of ATG7 expression and lipidation LC3B. Global miRNA expression profiling revealed 56 annotated and novel cardiac miRNAs exclusively dysregulated in female IUGR, and 38 cardiac miRNAs were exclusively dysregulated in males (p<0.05). Fifteen (CTRL) and 23 (IUGR) miRNAs, were differentially expressed between males and. females (p<0.05) suggesting sexual dimorphism, which can be at least partially explained by differential expression of upstream transcription factors (e.g. HNF4α, and NFκB p50). Lipidomics analysis of fetal cardiac tissue exhibited a net increase in diacylglycerol and plasmalogens and a decrease in triglycerides and phosphatidylcholines. In summary, IUGR resulting from decreased maternal nutrition is associated with sex-dependent dysregulations in cardiac structure, miRNA expression, and lipid metabolism. If these changes persist postnatally, they may program offspring for higher later life cardiac risk.

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Section: Resultsmentioning

confidence: 99%

Sexual dimorphism in the fetal cardiac response to maternal nutrient restriction

Muralimanoharan

Nakayasu

et al. 2017

Journal of Molecular and Cellular Cardiology

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“…Multiple clinical studies have been conducted to carefully characterize the miRNA profile in healthy versus advanced HF patients [146,147]. These clinical studies showed that miRNA profiles differ not only between HF and non-HF groups, but also between HF patients of differing ages and etiologies [129,148,149].…”

Section: Non-coding Rnasmentioning

confidence: 99%

Epigenetic regulation in heart failure

Kim

Morales

Gillette

et al. 2016

Current Opinion in Cardiology

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Purpose of review To provide an overview, highlighting recent findings, of a major mechanism of gene regulation and its relevance to the pathophysiology of heart failure. Recent findings The syndrome of heart failure is a complex and highly prevalent condition, one in which the heart undergoes substantial structural remodeling. Triggered by a wide range of disease-related cues, heart failure pathophysiology is governed by both genetic and epigenetic events. Epigenetic mechanisms, such as chromatin/DNA modifications and non-coding RNAs, have emerged as molecular transducers of environmental stimuli to control gene expression. Here, we emphasize metabolic milieu, aging, and hemodynamic stress as they impact the epigenetic landscape of the myocardium. Summary Recent studies in multiple fields, including cancer, stem cells, development, and cardiovascular biology, have uncovered biochemical ties linking epigenetic machinery and cellular energetics and mitochondrial function. Elucidation of these connections will afford molecular insights into long-established epidemiological observations. With time, exploitation of the epigenetic machinery therapeutically may emerge with clinical relevance.

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“…Two miRNAs, miR-624 and miR-339, were deregulated in ischemic heart disease and coronary artery disease [53, 54]. MiR-744 was deregulated in patients with chronic congestive heart failure [55]. Several miRNAs were detected in cardiac tissue at different stages of development and are highly expressed in the fetal heart, including miR-212, miR-210 and miR-423 [41].…”

Section: Discussionmentioning

confidence: 99%

Differential expression of microRNAs following cardiopulmonary bypass in children with congenital heart diseases

et al. 2017

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BackgroundChildren with congenital heart defects (CHDs) are at high risk for myocardial failure after operative procedures with cardiopulmonary bypass (CPB). Recent studies suggest that microRNAs (miRNA) are involved in the development of CHDs and myocardial failure. Therefore, the aim of this study was to determine alterations in the miRNA profile in heart tissue after cardiac surgery using CPB.MethodsIn total, 14 tissue samples from right atrium were collected from patients before and after connection of the CPB. SurePrint™ 8 × 60K Human v21 miRNA array and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) were employed to determine the miRNA expression profile from three patients before and after connection of the CPB. Enrichment analyses of altered miRNA expression were predicted using bioinformatic tools.ResultsAccording to miRNA array, a total of 90 miRNAs were significantly altered including 29 miRNAs with increased and 61 miRNAs with decreased expression after de-connection of CPB (n = 3) compared to before CPB (n = 3). Seven miRNAs had been validated using RT-qPCR in an independent cohort of 11 patients. Enrichment analyses applying the KEGG database displayed the highest correlation for signaling pathways, cellular community, cardiovascular disease and circulatory system.ConclusionOur result identified the overall changes of the miRNome in right atrium tissue of patients with CHDs after CPB. The differentially altered miRNAs lay a good foundation for further understanding of the molecular function of changed miRNAs in regulating CHDs and after CPB in particular.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1213-9) contains supplementary material, which is available to authorized users.

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The prognostic value of circulating microRNAs in heart failure

Abstract: We demonstrated the increased expression levels of circulating miRNAs in CHF as compared with controls. Moreover, miR-182 was found to be a potential prognostic marker in CHF.

Cited by 91 publications

References 26 publications

Sexual dimorphism in the fetal cardiac response to maternal nutrient restriction

Sexual dimorphism in the fetal cardiac response to maternal nutrient restriction

Epigenetic regulation in heart failure

Differential expression of microRNAs following cardiopulmonary bypass in children with congenital heart diseases

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