Przewratil Przemyslaw, Kobos Józef, Wnęk Aneta, Szemraj Janusz, Wyrzykowski Dariusz, Chrzanowska Barbara, Andrzejewska Ewa, Taran Katarzyna
Department of Pediatric Surgery and Oncology, Medical University of Lodz.
Department of Pathology, Medical University of Lodz.
Immunol Lett. 2016 Jul;175:44-9. doi: 10.1016/j.imlet.2016.05.002. Epub 2016 May 10.
In the last few years propranolol has revolutionized infantile hemangioma therapy. This nonselective β bloker has been proven to be safe and effective but the molecular bases of its actions remain unclear. One of debated theories holds that propranolol may inhibit angiogenesis and induce apoptosis. To investigate this claim, this study aims to analyze the serum and tissue profiles of VEGF and VEGRR1/2 in patients treated with propranolol.
To assess the expression if VEGF and VEGRR1/2 we used three independent methods. First we analyzed serum VEGF levels in 50 children with IH before and 3 months after the therapy using ELISA test (I.). Then we used immunohistochemistry to evaluate tissue expression of VEGF and VEGFR1/2 in IH treated (n=27) and not treated (n=45) with propranolol (II.). Finally we assessed mRNA of VEGF and VEGFR1/2 in the same patients as in part II (III.).
(I) There was no distinct decrease of VEGF level in children with IH after propranolol treatment. (II) We found no significant difference in VEGFR1 and VEGFR2 expression in hemangiomas from the study and control group. The expression of VEGF was even higher than before therapy. (III) VEGF and VEGFR1 mRNA expression was significantly lower in IH tissue after propranolol treatment compared to those without treatment. VEGFR2 demonstrated no differences in expression between the two groups.
The obtained results show distinct discrepancies between in vitro and clinical studies as well as among different methods used for analyzing the same phenomenon. Only VEGF and VEGFR1 expression in mRNA studies may prove the proposed theory of antiangiogenic properties of propranolol. Other results do not confirm it and remain inconsistent with the fantastic clinical response to this medication.
在过去几年中，普萘洛尔彻底改变了婴儿血管瘤的治疗方法。这种非选择性β受体阻滞剂已被证明是安全有效的，但其作用的分子基础仍不清楚。一个有争议的理论认为，普萘洛尔可能抑制血管生成并诱导细胞凋亡。为了研究这一说法，本研究旨在分析接受普萘洛尔治疗的患者中VEGF和VEGRR1/2的血清和组织谱。
为了评估VEGF和VEGRR1/2的表达，我们使用了三种独立的方法。首先，我们使用酶联免疫吸附测定法（I.）分析了50例婴儿血管瘤患儿治疗前和治疗3个月后的血清VEGF水平。然后，我们使用免疫组织化学方法评估普萘洛尔治疗（n = 27）和未治疗（n = 45）的婴儿血管瘤中VEGF和VEGFR1/2的组织表达（II.）。最后，我们评估了与第二部分相同患者中VEGF和VEGFR1/2的mRNA（III.）。
（I.）普萘洛尔治疗后，婴儿血管瘤患儿的VEGF水平没有明显下降。（II.）我们发现研究组和对照组血管瘤中VEGFR1和VEGFR2的表达没有显著差异。VEGF的表达甚至比治疗前更高。（III.）与未治疗的组织相比，普萘洛尔治疗后婴儿血管瘤组织中VEGF和VEGFR1 mRNA的表达显著降低。两组之间VEGFR2的表达没有差异。
获得的结果表明，体外研究和临床研究之间以及用于分析同一现象的不同方法之间存在明显差异。只有mRNA研究中VEGF和VEGFR1的表达可能证明普萘洛尔具有抗血管生成特性的理论。其他结果未证实这一点，并且与该药物出色的临床反应不一致。
