Faculty of Medicine, Institute of Pathophysiology, University of Nis, Nis, Serbia.
Institute for Treatment and Rehabilitation "Niska Banja", Niška Banja, Serbia.
Curr Med Res Opin. 2020 Jun;36(6):909-919. doi: 10.1080/03007995.2020.1756233. Epub 2020 Apr 29.
Heart failure (HF) represents a huge socio-economic burden. It has been demonstrated, experimentally, that renalase, a newly discovered protein, prevents cardiac hypertrophy and adverse remodeling, which is seen in HF. We postulated the following aims: to investigate associations of renalase with biomarkers of cardiac remodeling: galectin-3, soluble suppression of tumorigenicity, (sST2), growth differentiation factor 15 (GDF-15) and syndecan-1, myocardial stretch (BNP) and cardio-renal axis (cystatin C) in HF patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) to determine whether renalase, in combination with left ventricular ejection fraction (LVEF), represents a risk factor for plasma elevation in biomarkers. We classified HF patients ( = 76) according to LVEF (preserved/reduced), applied a median plasma renalase (113 ng/mL) as a cut-off value (low/high) and created four subgroups of HF patients: HFpEF/low renalase ( = 19), HFrEF/low renalase ( = 19), HFrEF/high renalase ( = 32) and HFpEF/high renalase ( = 6). A control group ( = 35) consisted of healthy volunteers. Plasma concentrations of evaluated biomarkers were determined using an ELISA technique and were highest in HF patients with reduced EF ( < .001, respectively), and renalase's positive correlations were obtained relating to all biomarkers: galectin-3 ( = 0.913; < .001), sST2 ( = 0.965; < .001), GDF-15 ( = 0.887; < .001), syndecan-1 ( = 0.922; < .001), BNP ( = 0.527; < .001) and cystatin C ( = 0.844; < .001) and strong and negative correlation with LVEF ( = -0.456, < .001). Increased renalase, regardless of the EF (preserved/reduced), was shown to be an independent risk factor for an increase in all evaluated cardiac remodeling biomarkers, < .001, respectively. However, increased renalase and reduced EF was the only independent risk factor for BNP and cystatin C elevation, < .001, respectively. Results after multivariable adjustments (age/gender) were identical. When elevated plasma renalase and HF are present, regardless of EF being reduced or preserved, that represents a significant risk factor for increase in cardiac remodeling biomarker plasma concentrations. However, only elevated renalase and reduced EF demonstrated significance as a risk factor for BNP and cystatin C plasma elevation. Renalase may be considered a promising molecule for the improved predictive abilities of conventional biomarkers and is worthy of further investigation.
心力衰竭（HF）是一个巨大的社会经济负担。实验已经证明，一种新发现的蛋白质肾酶可以预防心力衰竭中所见的心肌肥大和不良重构。我们提出了以下目的：研究肾酶与心肌重构生物标志物的相关性：半乳糖凝集素-3、可溶性肿瘤抑制物（sST2）、生长分化因子 15（GDF-15）和连接蛋白-1、心肌拉伸（BNP）和心肾轴（胱抑素 C）在射血分数降低的心力衰竭（HFrEF）和射血分数保留的心力衰竭（HFpEF）患者中的相关性，以确定肾酶是否与左心室射血分数（LVEF）联合起来是生物标志物血浆升高的危险因素。我们根据 LVEF（保留/降低）将心力衰竭患者（ = 76）分类，将中位数血浆肾酶（113 ng/mL）作为截断值（低/高），并创建了四个心力衰竭患者亚组：HFpEF/低肾酶（ = 19）、HFrEF/低肾酶（ = 19）、HFrEF/高肾酶（ = 32）和 HFpEF/高肾酶（ = 6）。一个对照组（ = 35）由健康志愿者组成。使用 ELISA 技术测定评估生物标志物的血浆浓度，在射血分数降低的心力衰竭患者中最高（ < .001），并且获得了肾酶与所有生物标志物之间的正相关关系：半乳糖凝集素-3（ = 0.913； < .001）、sST2（ = 0.965； < .001）、GDF-15（ = 0.887； < .001）、连接蛋白-1（ = 0.922； < .001）、BNP（ = 0.527； < .001）和胱抑素 C（ = 0.844； < .001），与 LVEF 呈强负相关（ = -0.456， < .001）。无论射血分数（保留/降低）如何，升高的肾酶均被证明是所有评估的心肌重构生物标志物升高的独立危险因素， < .001。然而，升高的肾酶和降低的 EF 是 BNP 和胱抑素 C 升高的唯一独立危险因素， < .001。经过多变量调整（年龄/性别）的结果是相同的。当存在升高的血浆肾酶和心力衰竭时，无论 EF 是降低还是保留，这都是心肌重构生物标志物血浆浓度升高的重要危险因素。然而，只有升高的肾酶和降低的 EF 被证明是 BNP 和胱抑素 C 血浆升高的危险因素。肾酶可能被认为是提高传统生物标志物预测能力的有前途的分子，值得进一步研究。
