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MicroRNA Expression in Myocardial Tissue and Plasma of Patients with End-Stage Heart Failure during LVAD Support: Comparison of Continuous and Pulsatile Devices.

Lok SI, de Jonge N, van Kuik J, van Geffen AJ, Huibers MM, van der Weide P, Siera E, Winkens B, Doevendans PA, de Weger RA, da Costa Martins PA - PLoS ONE (2015)

Bottom Line: Our aim was to analyze cardiac miR expression patterns associated with each type of device, to analyze differences in the regulation of the induced cardiac changes.Circulating miR-21 decreased at 1, 3, and 6 months after LVAD implantation.However, the miR expression patterns do not seem to significantly differ between pf- and cf-LVAD implying that most cardiac changes or clinical outcomes specific to each device do not relate to differences in miR expression levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, University Medical Center, Utrecht, the Netherlands; Department of Pathology, University Medical Center, Utrecht, the Netherlands.

ABSTRACT

Aim: Pulsatile flow left ventricular assist devices (pf-LVADs) are being replaced by continuous flow LVADs (cf-LVADs) in patients with end-stage heart failure (HF). MicroRNAs (miRs) play an important role in the onset and progression of HF. Our aim was to analyze cardiac miR expression patterns associated with each type of device, to analyze differences in the regulation of the induced cardiac changes.

Methods and results: Twenty-six miRs were selected (based on micro-array data and literature studies) and validated in myocardial tissue before and after pf- (n = 17) and cf-LVAD (n = 17) support. Of these, 5 miRs displayed a similar expression pattern among the devices (miR-129*, miR-146a, miR-155, miR-221, miR-222), whereas others only changed significantly during pf-LVAD (miR-let-7i, miR-21, miR-378, miR-378*) or cf-LVAD support (miR-137). In addition, 4 miRs were investigated in plasma of cf-LVAD supported patients (n = 18) and healthy controls (n = 10). Circulating miR-21 decreased at 1, 3, and 6 months after LVAD implantation. MiR-146a, miR-221 and miR-222 showed a fluctuating time pattern post-LVAD.

Conclusion: Our data show a different miR expression pattern after LVAD support, suggesting that differentially expressed miRs are partially responsible for the cardiac morphological and functional changes observed after support. However, the miR expression patterns do not seem to significantly differ between pf- and cf-LVAD implying that most cardiac changes or clinical outcomes specific to each device do not relate to differences in miR expression levels.

No MeSH data available.


Related in: MedlinePlus

Changes in plasma miR expression after continuous flow LVAD (cf-LVAD) implantation.Expression of circulating miR-21 (a), miR-146a (b), miR-221 (c) en miR-222 (d) during cf-LVAD support prior to and 1,3, and 6 months after implantation and before HTx (n = 18 patients) and controls (n = 10). In miR-222, no reliable duplicates on controls could be measured (d). The asterisk (*) represents p<0.05.
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pone.0136404.g003: Changes in plasma miR expression after continuous flow LVAD (cf-LVAD) implantation.Expression of circulating miR-21 (a), miR-146a (b), miR-221 (c) en miR-222 (d) during cf-LVAD support prior to and 1,3, and 6 months after implantation and before HTx (n = 18 patients) and controls (n = 10). In miR-222, no reliable duplicates on controls could be measured (d). The asterisk (*) represents p<0.05.

Mentions: 4 miRs that changed significantly in cf-LVAD supported patients were selected for further validation in plasma by Q-PCR: miR-21, miR-146a, miR-221 and miR-222. Prior to cf-LVAD implantation, levels of miR-21 were doubled compared to controls, decreased significantly during support, but did not normalize (Fig 3A). Levels of miR-146a were also increased in pre-LVAD compared to controls, but revealed a fluctuating expression pattern during support with a tendency to decrease (Fig 3B). The expression patterns for miR-221 and miR-222 were alike, with both miRs up-regulated after 1 month followed by down-regulation (Fig 3C and 3D). While for miR-21 the time response in expression levels was homogeneous between the different patients, for the other three microRNAs, the expression levels determined in a few patients (outliers, non-responders) are very discrepant from the rest of the group (Fig 3A–3D).


MicroRNA Expression in Myocardial Tissue and Plasma of Patients with End-Stage Heart Failure during LVAD Support: Comparison of Continuous and Pulsatile Devices.

Lok SI, de Jonge N, van Kuik J, van Geffen AJ, Huibers MM, van der Weide P, Siera E, Winkens B, Doevendans PA, de Weger RA, da Costa Martins PA - PLoS ONE (2015)

Changes in plasma miR expression after continuous flow LVAD (cf-LVAD) implantation.Expression of circulating miR-21 (a), miR-146a (b), miR-221 (c) en miR-222 (d) during cf-LVAD support prior to and 1,3, and 6 months after implantation and before HTx (n = 18 patients) and controls (n = 10). In miR-222, no reliable duplicates on controls could be measured (d). The asterisk (*) represents p<0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4592005&req=5

pone.0136404.g003: Changes in plasma miR expression after continuous flow LVAD (cf-LVAD) implantation.Expression of circulating miR-21 (a), miR-146a (b), miR-221 (c) en miR-222 (d) during cf-LVAD support prior to and 1,3, and 6 months after implantation and before HTx (n = 18 patients) and controls (n = 10). In miR-222, no reliable duplicates on controls could be measured (d). The asterisk (*) represents p<0.05.
Mentions: 4 miRs that changed significantly in cf-LVAD supported patients were selected for further validation in plasma by Q-PCR: miR-21, miR-146a, miR-221 and miR-222. Prior to cf-LVAD implantation, levels of miR-21 were doubled compared to controls, decreased significantly during support, but did not normalize (Fig 3A). Levels of miR-146a were also increased in pre-LVAD compared to controls, but revealed a fluctuating expression pattern during support with a tendency to decrease (Fig 3B). The expression patterns for miR-221 and miR-222 were alike, with both miRs up-regulated after 1 month followed by down-regulation (Fig 3C and 3D). While for miR-21 the time response in expression levels was homogeneous between the different patients, for the other three microRNAs, the expression levels determined in a few patients (outliers, non-responders) are very discrepant from the rest of the group (Fig 3A–3D).

Bottom Line: Our aim was to analyze cardiac miR expression patterns associated with each type of device, to analyze differences in the regulation of the induced cardiac changes.Circulating miR-21 decreased at 1, 3, and 6 months after LVAD implantation.However, the miR expression patterns do not seem to significantly differ between pf- and cf-LVAD implying that most cardiac changes or clinical outcomes specific to each device do not relate to differences in miR expression levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, University Medical Center, Utrecht, the Netherlands; Department of Pathology, University Medical Center, Utrecht, the Netherlands.

ABSTRACT

Aim: Pulsatile flow left ventricular assist devices (pf-LVADs) are being replaced by continuous flow LVADs (cf-LVADs) in patients with end-stage heart failure (HF). MicroRNAs (miRs) play an important role in the onset and progression of HF. Our aim was to analyze cardiac miR expression patterns associated with each type of device, to analyze differences in the regulation of the induced cardiac changes.

Methods and results: Twenty-six miRs were selected (based on micro-array data and literature studies) and validated in myocardial tissue before and after pf- (n = 17) and cf-LVAD (n = 17) support. Of these, 5 miRs displayed a similar expression pattern among the devices (miR-129*, miR-146a, miR-155, miR-221, miR-222), whereas others only changed significantly during pf-LVAD (miR-let-7i, miR-21, miR-378, miR-378*) or cf-LVAD support (miR-137). In addition, 4 miRs were investigated in plasma of cf-LVAD supported patients (n = 18) and healthy controls (n = 10). Circulating miR-21 decreased at 1, 3, and 6 months after LVAD implantation. MiR-146a, miR-221 and miR-222 showed a fluctuating time pattern post-LVAD.

Conclusion: Our data show a different miR expression pattern after LVAD support, suggesting that differentially expressed miRs are partially responsible for the cardiac morphological and functional changes observed after support. However, the miR expression patterns do not seem to significantly differ between pf- and cf-LVAD implying that most cardiac changes or clinical outcomes specific to each device do not relate to differences in miR expression levels.

No MeSH data available.


Related in: MedlinePlus