Department of Vascular Surgery, Turku University and Turku University Hospital, Turku, Finland.
Department of Vascular Surgery, Turku University and Turku University Hospital, Turku, Finland.
Cytokine. 2018 Oct;110:24-28. doi: 10.1016/j.cyto.2018.04.012. Epub 2018 Apr 23.
The aim of the present study was to assess the circulating levels of vascular endothelial growth factor (VEGF) and other suggested therapeutic growth factors with the degree of ischemia in patients with different clinical manifestations of peripheral arterial disease (PAD) according to the Rutherford grades.
The study cohort consists of 226 consecutive patients admitted to a Department of Vascular Surgery for elective invasive procedures. PAD patients were grouped according to the Rutherford grades after a clinical assessment. Ankle-brachial pressure indices (ABI) and absolute toe pressure (TP) values were measured. Serum levels of circulating VEGF, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and platelet derived growth factor (PDGF) were measured from serum and analysed against Rutherford grades and peripheral hemodynamic measurements.
The levels of VEGF (P = 0.009) and HGF (P < 0.001) increased significantly as the ischaemic burden became more severe according to the Rutherford grades. PDGF behaved in opposite manner and declined along increasing Rutherford grades (P = 0.004). A significant, inverse correlations between Rutherford grades was detected as follows; VEGF (Pearson's correlation = 0.183, P = 0.004), HGF (Pearson's correlation = 0.253, P < 0.001), bFGF (Pearson's correlation = 0.169, P = 0.008) and PDGF (Pearson's correlation = 0.296, P < 0.001). In addition, VEGF had a clear direct negative correlation with ABI (Pearson's correlation -0.19, P = 0.009) and TP (Pearson's correlation -0.20, P = 0.005) measurements.
Our present observations show that the circulating levels of VEGF and other suggested therapeutic growth factors are significantly increased along with increasing ischemia. These findings present a new perspective to anticipated positive effects of gene therapies utilizing VEGF, HGF, and bFGF, because the levels of these growth factors are endogenously high in end-stage PAD.
本研究的目的是评估血管内皮生长因子(VEGF)和其他有治疗作用的生长因子在不同临床表现的外周动脉疾病(PAD)患者中的循环水平,并根据 Rutherford 分级评估其与缺血程度的关系。
研究队列由 226 名连续因选择性有创性治疗而被收入血管外科的患者组成。PAD 患者根据 Rutherford 分级进行临床评估后分组。测量踝肱指数(ABI)和绝对趾压(TP)值。从血清中测量循环 VEGF、肝细胞生长因子(HGF)、碱性成纤维细胞生长因子(bFGF)和血小板衍生生长因子(PDGF)的水平,并根据 Rutherford 分级和外周血流动力学测量进行分析。
根据 Rutherford 分级,VEGF(P=0.009)和 HGF(P<0.001)水平随着缺血负担的加重而显著升高。PDGF 的行为则相反,随着 Rutherford 分级的增加而下降(P=0.004)。检测到 Rutherford 分级之间存在显著的负相关关系,如下所示:VEGF(皮尔逊相关系数=0.183,P=0.004)、HGF(皮尔逊相关系数=0.253,P<0.001)、bFGF(皮尔逊相关系数=0.169,P=0.008)和 PDGF(皮尔逊相关系数=0.296,P<0.001)。此外,VEGF 与 ABI(皮尔逊相关系数-0.19,P=0.009)和 TP(皮尔逊相关系数-0.20,P=0.005)测量值有明确的直接负相关关系。
我们目前的观察结果表明,随着缺血程度的增加,VEGF 和其他有治疗作用的生长因子的循环水平显著升高。这些发现为利用 VEGF、HGF 和 bFGF 进行基因治疗的预期积极效果提供了新的视角,因为在终末期 PAD 中,这些生长因子的水平是内源性升高的。