Serum Levels of Vascular Endothelial Growth Factor and Basic Fibroblastic Growth Factor in Children with Hemangiomas and Vascular Malformations—Preliminary Report

Abstract

Impaired balance between proangiogenic and antiangiogenic factors has been implicated in the development of hemangiomas. Elevated vascular endothelial growth factor serum levels and basic fibroblastic growth factor urine levels in patients with proliferating hemangiomas were reported. However, whether these growth factors can be used for the differential diagnosis of vascular anomalies or assessment of the clinical course of hemangiomas has yet to be determined. We report here our preliminary results of serum vascular endothelial growth factor and basic fibroblastic growth factor levels as an aid in the diagnosis of hemangiomas and in the follow up of patients with this lesion. Twenty two children with infantile hemangioma (13 with proliferating hemangiomas, nine with involuting lesions), five children with vascular malformations, and 25 healthy children study group. Vascular endothelial growth factor and basic fibroblastic growth factor serum levels were analyzed by an ELISA assay. The serum vascular endothelial growth factor concentrations in children with proliferating hemangiomas were significantly higher than in patients with involuting hemangiomas, vascular malformations and healthy patients. The serum basic fibroblastic growth factor concentrations were low and similar in all patients with no statistical correlation between study groups. We concluded that (i) ELISA can easily determine vascular endothelial growth factor concentrations in different phases of hemangioma growth and help distinguishing them from vascular malformations. (ii) A potential role for vascular endothelial growth factor in the pathophysiology of hemangiomas is probable.

Neuropilin-2 and vascular endothelial growth factor receptor-3 are up-regulated in human vascular malformations

“…Although VEGF-A and VEGFR-2 have been earlier related to the proliferating Hem [5][6][7][8] we did not see alterations in their gene expression levels. However, higher expression of VEGF-C and PlGF were found from venous type of VascM in comparison to other VascM and Hem.…”

“…In addition, two co-receptors, neuropilin (NRP)-1 and NRP2, have been identified [4]. In previous studies, increased circulating levels of VEGF-A have been found from patients with proliferating phase Hem in comparison to patients with involuting Hem or VascM [5,6]. Furthermore, decreased expression of VEGFR-1, and a missense mutation leading to the constitutive activity of VEGFR-2 and its downstream signaling cascade have been detected in some infantile Hem [7,8].…”

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?

“…Przewratil et al did not find a statistically significant difference in serum bFGF values in children with hemangiomas in the proliferative phase compared to the involuting phase. 19 In addition, no difference was observed between healthy children compared to children with a vascular malformation. Subsequent studies by the same author showed statistically significant lower values of serum bFGF in the proliferative phase (median bFGF values of 19.445 pg/mL) as compared to children with IH in the involuting phase (32.034 pg/mL).…”

“…A similar dependence was observed by other authors, although they found remarkably low levels of this factor in the material taken directly from the hemangioma, both in the proliferative phase and in the involution. 19,20 The proangiogenic properties of VEGF, as well as the effect of glucocorticoids on angiogenesis and vasculogenesis, have been reported in animal models. 21 After the implantation of stem cells producing vascular endothelial growth factor A (VEGF-A) in mice and simultaneous administration of dexamethasone, other researchers observed a decrease in VEGF value and symptoms of atrophic decompression.…”

Delivery of sodium morrhuate to hemangioma endothelial cells using immunoliposomes conjugated with anti-VEGFR2/KDR antibody

“…2 The life span of hemangiomas consists of proliferating phase, involuting phase, and involuted phase. 3,4 Although most hemangiomas can involute spontaneously, this process may take a long time and incur residual scars or pigmentary changes. 5 Deciphering the mechanisms governing hemangioma growth and progression is of significance in treating this disease.…”