VEGF-A, VEGFR-1, VEGFR-2 and Tie2 levels in plasma of premature infants:: relationship to retinopathy of prematurity

VEGF-A, VEGFR-1, VEGFR-2 and Tie2 levels in plasma of premature infants:: relationship to retinopathy of prematurity
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DOI:
10.1136/bjo.2007.128371
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发表时间:
2008-05-01
影响因子:
4.1
通讯作者:
Lagreze, W. A.
Lagreze, W. A.
中科院分区:
医学2区
文献类型:
--
作者:
Pieh, C.;Agostini, H.;Lagreze, W. A.

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目的:目的:前瞻性研究早产儿血浆血管内皮生长因子A(VEGF-A)及其可溶性受体sVEGFR-1、sVEGFR-2和可溶性Tie 2水平。方法:对63例早产儿(PMA)在出生后5天至15周内的外周血进行检测,分析其与早产儿视网膜病变(ROP)发病的关系。42名婴儿没有ROP,2名为1期,9名为2期,10名为3期。其中4名婴儿接受了视网膜光凝治疗。使用因子特异性单克隆小鼠抗体,通过夹心酶免疫测定法测定血浆中的VEGF-A、sVEGFR-1、sVEGFR-2和sTie 2。核平滑绘制的浓度的时间过程进行了比较,并与方差分析的配对亚组进行了analysed.Results:ROP患者的sVEGFR-2和sTie 2的血浆水平相比,早产儿没有ROP。两组的VEGF-A和sVEGFR-1水平相似。一个亚组的分析与对测量,一个在32周前和一个在36周后,显示了一个显着的增加sTie 2后36周的PMA独立的ROP(p = 0.03)。结论:这是第一个研究,以测量在ROP的血管生成因子的血浆水平。在患有和不患有ROP的婴儿中相似的VEGF-A血浆水平表明,ROP中的致病性视网膜血管生成主要由局部VEGF-A合成驱动。在活动性ROP中观察到sVEGFR-2和sTie 2的血浆水平升高。这些增加尚未被证实为ROP的预测值。
Aim: To study prospectively the plasma levels of vascular endothelial growth factor (VEGF-A), its soluble receptors sVEGFR-1, sVEGFR-2 and soluble Tie2 in premature infants. To identify their changes related to the onset of retinopathy of prematurity (ROP).Methods: Blood samples of 63 preterm infants born at a postmenstrual age (PMA) of 23-32 weeks were obtained between 5 days and 15 weeks after birth. 42 infants had no ROP, two had stage 1, nine stage 2 and 10 stage 3. Of these, four infants were treated with retinal photocoagulation. VEGF-A, sVEGFR-1, sVEGFR-2, and sTie2 were measured in the plasma with a sandwich enzyme immunoassay using factor-specific monoclonal mouse antibodies. The time course of concentrations plotted by kernel smoothing in infants with and without ROP were compared and a paired subgroup with analysis of variance was analysed.Results: ROP patients had raised plasma levels of sVEGFR-2 and sTie2 compared with premature infants without ROP. VEGF-A and sVEGFR-1 levels were similar in both groups. Analysis of a subgroup with pairs of measurements, one before 32 weeks and one after 36 weeks, showed a significant increase in sTie2 after 36 weeks of PMA independent of ROP (p = 0.03).Conclusion: This is the first study to measure plasma levels of angiogenic factors in ROP. Similar VEGF-A plasma levels in infants with and without ROP suggest that pathogenic retinal angiogenesis in ROP is mainly driven by local VEGF-A synthesis. Elevated plasma levels in active ROP were observed for sVEGFR-2 and sTie2. These increases have yet to be confirmed as predictive values for ROP.