Assessment of Plasma miRNAs in Congestive Heart Failure

Fukushima, Yasue; Nakanishi, Masayoshi; Nonogi, Hiroshi; Goto, Yoichi; Iwai, Naoharu

doi:10.1253/circj.cj-10-0457

Cited by 180 publications

(149 citation statements)

References 19 publications

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“…Increases in circulating miRNAs upon cell damage have been detected by RT-PCR-based approaches for liver, brain, and skeletal muscle (5), as well as heart (19,46 instances miRNAs even performed better than established protein biomarkers (5). Our analysis indicated that heart-specific myomirs performed similar to the highly sensitive cTnI assay, but we were unable to verify the utility of any recently proposed miRNA biomarker for HF (18,(20)(21)(22). Considering that sRNAseq experiments capture a wide spectrum of miRNAs as well as fragments of other classes of RNAs, and can be performed with low ng quantities of total RNA recoverable from 250 μL plasma or serum, this approach holds great potential for future RNA biomarker discovery.…”

Section: Discussionmentioning

confidence: 85%

“…S1) were shown to contribute to muscle or myocardial function (8, 9). miRNAs and other classes of RNA have been profiled in failing human myocardium (10)(11)(12)(13)(14)(15)(16)(17), and a selected subset was also investigated as circulating biomarkers in HF (18)(19)(20)(21)(22)(23)(24). However, in these studies heart tissue and circulating miRNA abundance changes were not acquired simultaneously to correlate changes in tissue versus circulating miRNA composition.…”

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confidence: 99%

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Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers

Akat

Moore-McGriff

Morozov

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

216

210

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Heart failure (HF) is associated with high morbidity and mortality and its incidence is increasing worldwide. MicroRNAs (miRNAs) are potential markers and targets for diagnostic and therapeutic applications, respectively. We determined myocardial and circulating miRNA abundance and its changes in patients with stable and end-stage HF before and at different time points after mechanical unloading by a left ventricular assist device (LVAD) by small RNA sequencing. miRNA changes in failing heart tissues partially resembled that of fetal myocardium. Consistent with prototypical miRNAtarget-mRNA interactions, target mRNA levels were negatively correlated with changes in abundance for highly expressed miRNAs in HF and fetal hearts. The circulating small RNA profile was dominated by miRNAs, and fragments of tRNAs and small cytoplasmic RNAs. Heart-and muscle-specific circulating miRNAs (myomirs) increased up to 140-fold in advanced HF, which coincided with a similar increase in cardiac troponin I (cTnI) protein, the established marker for heart injury. These extracellular changes nearly completely reversed 3 mo following initiation of LVAD support. In stable HF, circulating miRNAs showed less than fivefold differences compared with normal, and myomir and cTnI levels were only captured near the detection limit. These findings provide the underpinning for miRNA-based therapies and emphasize the usefulness of circulating miRNAs as biomarkers for heart injury performing similar to established diagnostic protein biomarkers.exRNA | body fluids | miRNA-mRNA regulation | development | cardiovascular disease

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Section: Discussionmentioning

confidence: 85%

mentioning

confidence: 99%

Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers

Akat

Moore-McGriff

Morozov

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

216

210

View full text Add to dashboard Cite

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“…Moreover, several other miRNAs including miR-92a (Loyer et al, 2014), miR-146a/b (Takahashi et al, 2010), miR-195 (Latranico et al, 2009, have been reported to have important regulatory roles in cardiovascular diseases. There are several miRNAs reported to have association with myocardial infarction (MI) like miR-126 associated with diabetes (Zampetaki et al, 2010), hyperlipodemia and age (Fukushima et al, 2011) the high levels of presence makes the patients with 2.7 fold higher risks of MI. On the other hand lower levels of miR-223 associated with diabetes (Zampetaki et al, 2010) is reported with high risks of MI.…”

Section: Sumoylation and Inflammatory Pathwaymentioning

confidence: 99%

SUMOylation: A link to future therapeutics

2016

Current Issues in Molecular Biology

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SUMOylation, much of a similar process like ubiquitination catches attention across various research groups as a potential therapeutic target to fight various infectious and cancerous diseases. This idea take its strength from recent reports which unearth the molecular mechanisms of SUMOylation and its involvement in important diseases distributed across various kingdoms. At the beginning SUMOylation was considered a process affected only by viral diseases but subsequent reports enlighten its role in diseases caused by bacteria as well. This enhances the SUMOylation canvas and demanded more in-depth study of the process. The present review is an attempt to study the regulatory mechanism of genes when the natural SUMOylation pathway is disturbed, the cross-talk among SUMOylation and other post translational modifications, the role of miRNAs in controlling the function of transcripts, loading of RNA species into exosomes and the possible SUMOylation related therapeutic targets. IntroductionThe innate immune responses across kingdoms are tightly regulated to fight attacking pathogens. Post translational modification of proteins like acetylation, methylation, ubiquitination and SUMOylation have predominant role in activation/deactivation of immune responses by regulating various cellular processes including transcription, DNA repair, proliferation and apoptosis as these have the potential to relocate the protein to different organelles and modify its biological function. The deep understanding of those post translational mechanisms could provide insights in controlling several disease conditions and develop therapeutics based on those post translational modification markers.The small ubiquitin like modifiers (SUMO) proteins discovered in 1997 (Mahajan et al., 1997) has since been recognized as family of important modification proteins unlike ubiquitination which is involved in degradation of proteins, instead it modulates the function of target proteins. The covalent conjugation of SUMO molecules to protein residue lysine on a typical consensus sequence ψKxD/E (where ψ is large hydrophobic residue, K is the target lysine, D/E is acidic residue and x represent any amino acid) (Rodriguez et al., 2001;Sampson et al., 2001). The process of SUMOylation is carried out by a cascade of three enzymes (E1, E2 and E3). E1 is a SUMO activating enzyme SAE1, while E2 is conjugating enzyme e.g. Ubc9 and E3 is SUMO ligase. The SUMOylation reaction is reversed by SENPs termed as deSUMOylation having distinct regulatory roles. Till date four SUMO molecules have been reported in mammals viz., SUMO1, SUMO2, SUMO3 and SUMO4. The sequence similarity of SUMO2 and SUMO3 are almost 97% hence are often reported collectively as SUMO2/3. Various kinds of stimuli like oxidative stress often increase the rate of SUMOylation. A recent report shows the exposure to cigarette smoke alters the microRNA expression by SUMOylation of DICER (Gross et al., 2014). Viruses and chemical toxins also causes an increase in SUMOylation, a well known exam...

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“…D'autres miARN (miR-18, miR-19) ont été impliqués dans le vieillissement et l'insuffisance cardiaque mais leurs mécanismes d'action restent encore mal définis [39]. Chez l'homme, différentes études ont tenté d'identifier des miARN circulants dans le sang périphérique, comme biomarqueurs de pathologies et du vieillissement cardiaques [31,34,[40][41][42]. Bien que les niveaux plasmatiques de certains miARN sont effectivement modifiés chez les sujets présentant des pathologies cardiaques, leur signification en termes physiopathologique (insuffisance cardiaque et vieillissement accéléré) et diagnostique nécessite d'être précisée [53].…”

Section: Rôle Des Petits Arn Non Codant Miarnunclassified