Przemyslaw Przewratil1, Józef Kobos2, Aneta Wnęk3, Janusz Szemraj4, Dariusz Wyrzykowski5, Barbara Chrzanowska5, Ewa Andrzejewska3, Katarzyna Taran2. 1. Department of Pediatric Surgery and Oncology, Medical University of Lodz. Electronic address: przemyslaw.przewratil@umed.lodz.pl. 2. Department of Pathology, Medical University of Lodz. 3. Department of Pediatric Surgery and Oncology, Medical University of Lodz. 4. Department of Biochemistry, Medical University of Lodz. 5. Department of Pediatric Surgery and Urology, Medical University of Gdańsk.
Abstract
UNLABELLED: 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. MATERIALS AND METHODS: 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.). RESULTS: (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. CONCLUSIONS: 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.
UNLABELLED: 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. MATERIALS AND METHODS: 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.). RESULTS: (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. CONCLUSIONS: 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.