Serum‐Level Changes of Vascular Endothelial Growth Factor in Children with Infantile Hemangioma after Oral Propranolol Therapy

Abstract

Oral propranolol is the first-line therapy for infantile hemangioma (IH), but its mechanism of action remains unclear. The aim of this study was to evaluate the change in serum vascular endothelial growth factor (VEGF) levels in patients with IH who underwent propranolol treatment. The study included 22 patients with IH receiving propranolol treatment. At three time points-before treatment and 1 and 3 months after treatment-blood samples were examined by enzyme-linked immunosorbent assay for serum VEGF expression. The mean serum VEGF concentration in children with proliferative hemangiomas was 395.0 ± 176.7 pg/mL, approximately twice as high as in patients with venous malformations (mean 170.7 pg/mL) and in healthy controls (204.8 pg/mL, p = 0.006). After 1 month of propranolol treatment, the level had fallen 21.6% (p = 0.003), although the downward trend was less obvious after 3 months of treatment (18.0%, p = 0.63). VEGF expression correlated significantly with the lesion size (correlation coefficient [R] = 0.43, p = 0.046), whereas no correlation was observed with age (R = 0.13, p = 0.56). Serum VEGF levels were higher in patients with IH and fell after 1 month of oral propranolol treatment. Similar results, although less pronounced, were found after 3 months of treatment. Lesion volume and serum level of VEGF were significantly correlated.

Serum and tissue profile of VEGF and its receptors VGFR1/R2 in children with infantile hemangiomas on systemic propranolol treatment

“…Zhang found elevated VEGF levels in hemangioma patients in comparison to those with vascular malformations [23]. There are also two clinical studies from China showing that VEGF and eNOS serum levels were lower after 1, 2 and 3 months of propranolol treatment [19,20]. However in one study the difference after 1 month was statistically insignificant (p = 0.365).…”

“…Authors' aim was to analyze the profile of VEGF serum levels and tissue expression of VEGF and VEGFR1/2 in children with IH treated with propranolol. We know, from very few publications, that serum levels of this cytokine is reduced after 1 and 3 months of therapy [19,20]. Analysis of tissue expression of protein and mRNA in the tumor was performed probably for the first time.…”

Serum concentrations of VEGF and bFGF in the course of propranolol therapy of infantile hemangioma in children: Are we closer to understand the mechanism of action of propranolol on hemangiomas?

“…Similar results were obtained by Chinese researchers. 24,25 The importance of bFGF in the proliferation and suppression of apoptosis of cells in the period of involution are to be emphasized. High concentrations are reported in the urine of patients with hemangiomas, whereas the decrease in urinary values is observed during treatment with interferon alpha 2.…”

Vascular Tumors/Birthmarks

“…[ 122 ] Decreased serum VEGF level in propranolol-treated hemangioma patients within fi rst month of treatment [ 123 ] G0/G1 phase cell cycle arrest of hemangioma endothelial cell proliferation ?ERK signaling downregulation, interference with VEGF-R-mediated hemangioma endothelial proliferation [ 124 ] Hemangioma-derived endothelial cell apoptosis, decreased VEGF expression [ 125 ] Inhibition of endothelial progenitor cell homing [ 124 , 126 ] Apoptosis induction via activation of the intrinsic and extrinsic apoptotic pathways [ 124 , 127 ] Growth inhibition, not apoptosis of hemangioma cells [ 128 ] …”