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循环生长因子在主动脉瓣狭窄中的预后效用:一项初步研究。

Prognostic Utility of Circulating Growth Factors in Aortic Valve Stenosis: A Pilot Study.

作者信息

Hofmanis Juris, Tretjakovs Peteris, Svirskis Simons, Gersone Gita, Hofmane Dace, Rozenberga Ulla, Blumfelds Leons, Bahs Guntis, Lejnieks Aivars, Mackevics Vitolds

机构信息

Faculty of Medicine, Riga Stradins University, 16 Dzirciema Str., LV-1007 Riga, Latvia.

出版信息

Medicina (Kaunas). 2021 Jan 18;57(1):78. doi: 10.3390/medicina57010078.

Abstract

: 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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f766/7831117/63e04f054868/medicina-57-00078-g001.jpg

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