Evaluation of Effect of Propranolol on Serum Vascular Endothelial Growth Factor and Tissue Inhibitor of Metalloproteinase-2 Levels in Infantile Hemangioma

Background: Infantile hemangioma is the most common tumor of infancy. Currently, propranolol is a preferred drug for treating hemangioma. The exact mechanism of action of propranolol is not known. In this study, we attempted to assess whether propranolol has any effect on vascular endothelial growth factor (VEGF) and tissue inhibitor of metalloproteinase-2 (TIMP-2) over a period of time, and if it is there, how long it affects it. Materials and Methods: Propranolol was administered in the dosage of 2–3 mg/kg. The first serum sample was collected before starting the propranolol treatment. Thereafter, samples were collected at monthly intervals up to a total of six samples. The samples were assessed for TIMP-2 and VEGF using enzyme-linked immunosorbent assay kit. Results: The duration of this study was from June 2016 to November 2017. The total number of patients in this study was 15. Thirteen patients responded to treatment. The mean age of patients was 7.1 months. The mean value of baseline VEGF was 0.234 ± 0.059 and that of TIMP-2 was 1.338 ± 0.679. As compared to baseline value, the P value was statistically not significant in any of sequential values. In category-wise analysis, apart from statistically significant value in the 6th month in excellent category and good response category in the 1st month, all other values did not reveal any significant change in VEGF analysis. The analysis of TIMP-2 revealed a significant change in the levels from Sample 2 to Sample 6 in the excellent response group; however, the levels did not show a specific trend either increasing or decreasing. Conclusion: Despite its beneficial action in regression of hemangioma, the exact mechanism is yet to be identified. The exact duration of treatment needs further evaluation.

[1]  E. Roé,et al.  Efficacy of Propranolol Between 6 and 12 Months of Age in High-Risk Infantile Hemangioma , 2018, Pediatrics.

[2]  Liangrong Zheng,et al.  Beta-adrenoceptor Activation by Norepinephrine Enhances Lipopolysaccharide-induced Matrix Metalloproteinase-9 Expression Through the ERK/JNK-c-Fos Pathway in Human THP-1 Cells , 2017, Journal of atherosclerosis and thrombosis.

[3]  E. Andrzejewska,et al.  Serum and tissue profile of VEGF and its receptors VGFR1/R2 in children with infantile hemangiomas on systemic propranolol treatment. , 2016, Immunology letters.

[4]  Lifen Chen,et al.  Clinical efficacy of propranolol in the treatment of hemangioma and changes in serum VEGF, bFGF and MMP-9. , 2015, Experimental and therapeutic medicine.

[5]  M. Vikkula,et al.  Molecular and Genetic Aspects of Hemangiomas and Vascular Malformations , 2015 .

[6]  C. Léauté-Labrèze Propanolol and Beta-Blockers in the Medical Treatment of Infantile Hemangiomas , 2015 .

[7]  L. Jie,et al.  [Expression of serum and urinary vascular endothelial growth factor-A and epidermal growth factor-like domain 7 in proliferating hemangioma treated with propranolol]. , 2014, Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology.

[8]  Lei Xue,et al.  Propranolol given orally for proliferating infantile haemangiomas: analysis of efficacy and serological changes in vascular endothelial growth factor and endothelial nitric oxide synthase in 35 patients. , 2013, The British journal of oral & maxillofacial surgery.

[9]  Hui Chen,et al.  Serum‐Level Changes of Vascular Endothelial Growth Factor in Children with Infantile Hemangioma after Oral Propranolol Therapy , 2013, Pediatric dermatology.

[10]  I. Dähnert,et al.  Role of connexins in infantile hemangiomas , 2013, Front. Pharmacol..

[11]  S. Fishman,et al.  Chapter 125 – Vascular Anomalies , 2012 .

[12]  R. Huo,et al.  [The change of serum vascular endothelial growth factor and matrix metalloproteinases-9 in proliferative hemangioma treated with propranolol]. , 2011, Zhonghua zheng xing wai ke za zhi = Zhonghua zhengxing waike zazhi = Chinese journal of plastic surgery.

[13]  E. Andrzejewska,et al.  Local serum levels of vascular endothelial growth factor in infantile hemangioma: intriguing mechanism of endothelial growth. , 2010, Cytokine.

[14]  S. Friedlander,et al.  Twenty years' experience of steroids in infantile hemangioma—a developing country's perspective , 2010 .

[15]  E. Andrzejewska,et al.  Serum Levels of Vascular Endothelial Growth Factor and Basic Fibroblastic Growth Factor in Children with Hemangiomas and Vascular Malformations—Preliminary Report , 2009, Pediatric dermatology.

[16]  F. Boralevi,et al.  Propranolol for severe hemangiomas of infancy. , 2008, The New England journal of medicine.

[17]  G. Gurtner,et al.  Hypoxia-Induced Mediators of Stem/Progenitor Cell Trafficking Are Increased in Children With Hemangioma , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[18]  Chihiro Kondo,et al.  Tissue inhibitors of metalloproteinases-1 (TIMP-1) and -2(TIMP-2) are major serum factors that stimulate the TIMP-1 gene in human gingival fibroblasts. , 2006, Biochimica et biophysica acta.

[19]  M. Mihm,et al.  Infantile hemangiomas are arrested in an early developmental vascular differentiation state , 2004, Modern Pathology.

[20]  W. Stetler-Stevenson,et al.  Inhibition of matrix metalloproteinases by over‐expression of tissue inhibitor of metalloproteinase‐2 inhibits the growth of experimental hemangiomas , 2001, International journal of cancer.

[21]  S. Peters,et al.  Steroid Therapy of a Proliferating Hemangioma: Histochemical and Molecular Changes , 2000, Pediatrics.

[22]  J. Mulliken,et al.  Cellular markers that distinguish the phases of hemangioma during infancy and childhood. , 1994, The Journal of clinical investigation.