Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
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.
Int J Cardiol. 2021 Sep 15;339:138-143. doi: 10.1016/j.ijcard.2021.06.050. Epub 2021 Jun 29.
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.
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.
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.
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.
目前一代左心室辅助装置（LVAD）在治疗终末期心力衰竭（HF）中的植入，不仅改善 HF 症状和终末器官灌注，而且还导致细胞和分子反应，推测是对这些装置产生的连续流的反应。MicroRNAs（miRNAs）是多个生物学过程中基因表达的重要转录后调节因子，包括 HF 的发病机制。在我们的研究中，我们研究了长期 LVAD 支持对血浆中流量敏感 miRNAs 变化的影响。
收集 33 例终末期心力衰竭患者（年龄 55.7±11.6 岁）的血液样本，分别在 LVAD 植入前和植入后 3、6、9 和 12 个月采集。使用定量 PCR 测量血浆中流量敏感 miRNAs；miR-10a、miR-10b、miR-146a、miR-146b、miR-663a、miR-663b、miR-21、miR-155 和 miR-126 的水平。
LVAD 植入后每次随访时，miR-126（P<0.03）和 miR-146a（P<0.02）的含量都增加。miR-155 与 Belcaro 评分呈正相关（P<0.04），miR-126 与内皮功能呈负相关，表现为反应性充血指数（P<0.05）。
我们的观察表明，LVAD 植入后，低脉动流上调了循环血流敏感 miRNAs 的血浆水平，导致内皮功能障碍和血管重塑。
