Hofmanis Juris, Tretjakovs Peteris, Svirskis Simons, Gersone Gita, Hofmane Dace, Rozenberga Ulla, Blumfelds Leons, Bahs Guntis, Lejnieks Aivars, Mackevics Vitolds
Faculty of Medicine, Riga Stradins University, 16 Dzirciema Str., LV-1007 Riga, Latvia.
Medicina (Kaunas). 2021 Jan 18;57(1):78. doi: 10.3390/medicina57010078.
: Aortic valve stenosis (AS) develops with a pronounced local inflammatory response, where a variety of growth factors are involved in the process, and may have a pro-inflammatory and anti-inflammatory effect. The aim of our study was to elucidate whether circulating growth factors: growth differentiation factor 15 (GDF-15), angiopoietin-2 (Ang-2), vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2), and fibroblast growth factor 21 (FGF-21) could be proposed as clinically relevant biomarkers to improve risk stratification in AS patients. : AS patients were classified into three groups: 16 patients with mild AS stenosis; 19 with moderate and 11 with severe AS, and 30 subjects without AS (echocardiographically approved) were selected as a control group. GDF-15, Ang-2, VEGF-A, FGF-2, and FGF-21 were measured in plasma by the ELISA method. : GDF-15 levels differed significantly not only when comparing AS patients with control groups ( < 0.0001), but also a statistically significant difference was achieved when comparing AS patients at a mild degree stage with control individuals. We found a strong relationship of GDF-15 levels regarding AS severity degree ( < 0.0001). VEGF-A, FGF-2 and FGF-21 levels were significantly higher in AS patients than in controls, but relationships regarding the AS severity degree were weaker ( < 0.02). ROC analysis of the study growth factors showed that GDF-15 might serve as a specific and sensitive biomarker of AS stenosis (AUC = 0.75, = 0.0002). FGF-21 correlated with GDF-15, Ang-2, and FGF-2, but it did not reach the level to serve as a clinically relevant biomarker of AS stenosis. AS is associated with significantly increased GDF-15, VEGF-A, FGF-2, and FGF-21 levels in plasma, but only GDF-15 shows a pronounced relationship regarding AS severity degree, and GDF-15 might serve as a specific and sensitive biomarker of AS stenosis.
主动脉瓣狭窄（AS）的发生伴随着明显的局部炎症反应，多种生长因子参与其中，且可能具有促炎和抗炎作用。我们研究的目的是阐明循环生长因子：生长分化因子15（GDF - 15）、血管生成素 - 2（Ang - 2）、血管内皮生长因子A（VEGF - A）、成纤维细胞生长因子2（FGF - 2）和成纤维细胞生长因子21（FGF - 21）是否可作为临床相关生物标志物以改善AS患者的风险分层。将AS患者分为三组：16例轻度AS狭窄患者；19例中度和11例重度AS患者，选取30例无AS（经超声心动图证实）的受试者作为对照组。采用酶联免疫吸附测定（ELISA）法检测血浆中的GDF - 15、Ang - 2、VEGF - A、FGF - 2和FGF - 21。GDF - 15水平不仅在比较AS患者与对照组时存在显著差异（<0.0001），而且在比较轻度AS患者与对照个体时也有统计学意义上的显著差异。我们发现GDF - 15水平与AS严重程度密切相关（<0.0001）。AS患者的VEGF - A、FGF - 2和FGF - 2水平显著高于对照组，但与AS严重程度的相关性较弱（<0.02）。对研究中的生长因子进行的ROC分析表明，GDF - 15可能是AS狭窄的特异性和敏感生物标志物（曲线下面积[AUC]=0.75，P = 0.0002）。FGF - 21与GDF - 15、Ang - 2和FGF - 2相关，但未达到可作为AS狭窄临床相关生物标志物的水平。AS与血浆中GDF - 15、VEGF - A、FGF - 2和FGF - 21水平显著升高相关，但只有GDF - 15与AS严重程度有显著关系，且GDF - 15可能是AS狭窄的特异性和敏感生物标志物。
