Dana Dlouha1, Peter Ivak2, Ivan Netuka3, Sarka Novakova1, Miroslav Konarik4, Zuzana Tucanova4, Vera Lanska5, Daniel Hlavacek6, Peter Wohlfahrt7, Jaroslav A Hubacek8, Jan Pitha1. 1. Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 2. 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. 3. 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. 4. Department of Cardiovascular Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 5. Statistical Unit, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 6. 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. 7. 3rd Department of Internal Medicine, 1st Faculty of Medicine, Charles University, Prague, Czech Republic. 8. 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.
Abstract
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.
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.
Authors: Taiyo Kuroda; Takuma Miyamoto; Chihiro Miyagi; Anthony R Polakowski; Christine R Flick; Barry D Kuban; George B Voros; Kimberly Such; Kiyotaka Fukamachi; Jamshid H Karimov Journal: Artif Organs Date: 2022-03-31 Impact factor: 2.663