CNR Clinical Physiology Institute, Pisa, Italy.
Department of Cardiac Surgery, Niguarda Ca' Granda Hospital, Milan, Italy; Department of Cardiac Surgery, AOU Bologna, S. Orsola Hospital, Italy.
Int J Cardiol. 2020 May 1;306:109-115. doi: 10.1016/j.ijcard.2020.02.058. Epub 2020 Feb 24.
Left ventricular assist devices (LVAD) are implanted in patients with end-stage heart failure (ESHF) as a mechanical support for the failing myocardium, which is characterized by an activation of the neuro-hormonal system, with release of vasoactive mediators, such as endothelin (ET)-1 and relaxin (RLX)-2. The aim of this study was to evaluate whether LVAD is able to modulate the RLX-2 and ET-1 system expression in ESHF patients.
Cardiac tissue was collected from ESHF patients before LVAD implantation (pre-LVAD group, n = 22), at the time of cardiac transplantation with concomitant LVAD removal (post-LVAD group, n = 6), and from stable HF patients on medical therapy at the time of cardiac transplantation (HTx group, n = 7). The expression of RLX-2, ET-1 system and inflammatory markers (IL-8, IL-6, TNF-α) were evaluated by Real-Time PCR.
RLX-2 mRNA resulted similar in pre-LVAD and HTx, but it was significantly increased in post-LVAD (p = 0.02/p = 0.01 respectively). A similar trend was observed for ET-1 and ET-converting enzyme (ECE)-1 while no significant difference was observed for ET-receptors. A positive correlation was found between ET-1 and ET-A (p = 0.031) and ECE-1 (p < 0.0001). The inflammatory markers resulted activated in all the three groups. A significant correlation between RLX-2 and ET-1 in pre-LVAD, as well as between RLX-2 and IL-8/IL-6, was found.
Our research investigates for the first time the involvement of RLX-2 and ET-1 system in ESHF patients supported by LVAD, demonstrating their potential ability to partially recover the failing myocardium, indicating their possible clinical role as biomarkers or pharmacological agents in LVAD patients.
The study of novel biomarkers in patients supported by continuous axial flow devices may be a starting point analysis applicable to patients with centrifugal flow devices.
左心室辅助装置（LVAD）被植入终末期心力衰竭（ESHF）患者体内，作为衰竭心肌的机械支持，其特征为神经激素系统的激活，血管活性介质如内皮素（ET）-1 和松弛素（RLX）-2 的释放。本研究旨在评估 LVAD 是否能够调节 ESHF 患者的 RLX-2 和 ET-1 系统表达。
在 LVAD 植入前（预 LVAD 组，n=22）、同期 LVAD 移除时进行心脏移植（后 LVAD 组，n=6）和心脏移植时接受药物治疗的稳定 HF 患者（HTx 组，n=7）时，从 ESHF 患者心脏组织中采集 RLX-2、ET-1 系统和炎症标志物（IL-8、IL-6、TNF-α）的表达。通过实时 PCR 评估 RLX-2、ET-1 系统和炎症标志物的表达。
预 LVAD 和 HTx 组的 RLX-2mRNA 相似，但在后 LVAD 组显著增加（p=0.02/p=0.01）。ET-1 和 ET 转换酶（ECE）-1 也呈现类似趋势，而 ET 受体则无显著差异。ET-1 与 ET-A（p=0.031）和 ECE-1（p<0.0001）之间存在正相关。所有三组的炎症标志物均被激活。在预 LVAD 组中发现 RLX-2 与 ET-1 之间存在显著相关性，以及 RLX-2 与 IL-8/IL-6 之间存在显著相关性。
我们的研究首次调查了 RLX-2 和 ET-1 系统在 LVAD 支持的 ESHF 患者中的参与情况，证明了它们部分恢复衰竭心肌的潜在能力，表明它们作为生物标志物或药物在 LVAD 患者中的潜在临床作用。
文中缩写：LVAD（左心室辅助装置）、ESHF（终末期心力衰竭）、RLX-2（松弛素 2）、ET-1（内皮素 1）、HTx（心脏移植）、IL-8（白细胞介素 8）、IL-6（白细胞介素 6）、TNF-α（肿瘤坏死因子-α）、ECE-1（ET 转换酶 1）
术语翻译：
“neuro-hormonal system”翻译为“神经激素系统”；
“vasoactive mediators”翻译为“血管活性介质”；
“biological markers”翻译为“生物标志物”；
“pharmacological agents”翻译为“药物”。
