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The effect of long-term left ventricular assist device support on flow-sensitive plasma microRNA levels

D. Dlouha, P. Ivak, I. Netuka, S. Novakova, M. Konarik, Z. Tucanova, V. Lanska, D. Hlavacek, P. Wohlfahrt, JA. Hubacek, J. Pitha

. 2021 ; 339 (-) : 138-143. [pub] 20210629

Language English Country Netherlands

Document type Journal Article

Grant support
NV16-27630A MZ0 CEP Register

BACKGROUND: Implantation of current generation left ventricular assist devices (LVADs) in the treatment of end-stage heart failure (HF), not only improves HF symptoms and end-organ perfusion, but also leads to cellular and molecular responses, presumably in response to the continuous flow generated by these devices. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression in multiple biological processes, including the pathogenesis of HF. In our study, we examined the influence of long-term LVAD support on changes in flow-sensitive miRNAs in plasma. MATERIALS AND METHODS: Blood samples from patients with end-stage heart failure (N = 33; age = 55.7 ± 11.6 years) were collected before LVAD implantation and 3, 6, 9, and 12 months after implantation. Plasma levels of the flow-sensitive miRNAs; miR-10a, miR-10b, miR-146a, miR-146b, miR-663a, miR-663b, miR-21, miR-155, and miR-126 were measured using quantitative PCR. RESULTS: Increasing quantities of miR-126 (P < 0.03) and miR-146a (P < 0.02) was observed at each follow-up visit after LVAD implantation. A positive association between miR-155 and Belcaro score (P < 0.04) and an inverse correlation between miR-126 and endothelial function, measured as the reactive hyperemia index (P < 0.05), was observed. CONCLUSIONS: Our observations suggest that after LVAD implantation, low pulsatile flow up-regulates plasma levels of circulating flow-sensitive miRNAs, contributing to endothelial dysfunction and vascular remodeling.

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$a BACKGROUND: Implantation of current generation left ventricular assist devices (LVADs) in the treatment of end-stage heart failure (HF), not only improves HF symptoms and end-organ perfusion, but also leads to cellular and molecular responses, presumably in response to the continuous flow generated by these devices. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression in multiple biological processes, including the pathogenesis of HF. In our study, we examined the influence of long-term LVAD support on changes in flow-sensitive miRNAs in plasma. MATERIALS AND METHODS: Blood samples from patients with end-stage heart failure (N = 33; age = 55.7 ± 11.6 years) were collected before LVAD implantation and 3, 6, 9, and 12 months after implantation. Plasma levels of the flow-sensitive miRNAs; miR-10a, miR-10b, miR-146a, miR-146b, miR-663a, miR-663b, miR-21, miR-155, and miR-126 were measured using quantitative PCR. RESULTS: Increasing quantities of miR-126 (P < 0.03) and miR-146a (P < 0.02) was observed at each follow-up visit after LVAD implantation. A positive association between miR-155 and Belcaro score (P < 0.04) and an inverse correlation between miR-126 and endothelial function, measured as the reactive hyperemia index (P < 0.05), was observed. CONCLUSIONS: Our observations suggest that after LVAD implantation, low pulsatile flow up-regulates plasma levels of circulating flow-sensitive miRNAs, contributing to endothelial dysfunction and vascular remodeling.
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$a Ivak, Peter $u Department of Cardiovascular Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.; Department of Physiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic; Second Department of Surgery, Department of Cardiovascular Surgery, First Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address: peter.ivak@ikem.cz
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$a Netuka, Ivan $u Department of Cardiovascular Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.; Second Department of Surgery, Department of Cardiovascular Surgery, First Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Novakova, Sarka $u Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
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$a Konarik, Miroslav $u Department of Cardiovascular Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
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$a Tucanova, Zuzana $u Department of Cardiovascular Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
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$a Lanska, Vera $u Statistical Unit, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
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$a Hlavacek, Daniel $u Department of Cardiovascular Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.; Department of Physiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Wohlfahrt, Peter $u 3rd Department of Internal Medicine, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Hubacek, Jaroslav A $u Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.; 3rd Department of Internal Medicine, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Pitha, Jan $u Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
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