The Expression And Role Of β-AR Subtypes, VEGF And VEGFR-2in Infantile Hemangioma

Objective: Infantile hemangioma (IH) is a benign vascular neoplasm thatarises from the abnormal proliferation of hemangioma endothelial cells(HemEC) and enhanced angiogenesis. Angiogenesis is mediated by multiplesignaling pathways, in which VEGF-VEGFR-2is one of the most importantsignaling pathways, and plays an important role in hemangioma development.Propranolol, a non-selective β-adrenergic receptor (β-AR) blocker, had beenfound to be obviously effective in the management of IH. But its exactmechanism is unclear. β-AR including β1-AR,β2-AR and β3-AR subtype.β-AR, VEGF and VEGFR-2are closely relative in hemangioma hyperplasia,but comprehensive study about them is rarely reported. Therefore, thisexperiment explored the effect and role of β-AR,VEGF and VEGFR-2in thedevelopment of infantile hemangiomas by detecting the expression ofβ-AR,VEGF and VEGFR-2in hemangiomas, vascular malformations andnormal skins closing to hemangioma, to provide a theoretical basis for clinicaltreatment. Methods: From the Department of Pathology, Affiliated Hospital ofLuzhou Medical College during2012/2and2013/12, the specimens embeddedin paraffin of hemangioma group(45cases) were collected, and vascularmalformations(20cases) and normal skins closing to hemangioma (10cases)were chosen as control groups.We classified the hemangioma’s specimens into proliferating stage (23cases) and involuting stage(22cases) in the light of theMulliken’s classification standard. The expression of β-AR,VEGF andVEGFR-2was detected by two-step immunohistochemical technique in allgroups, and we recorded their numbers and grades of positive cells bysemi-quantitative analysis. Results:1.The expression of β1-AR and β3-AR arenegative or weakly positive in all groups. The three groups had no statisticalsignificance (P>0.05). There were significant difference of β2-AR expressionamong three groups(P<0.05). But in vascular malformations and normal skinsis weakly positive or negative, without significance (P>0.05). The positiveexpression of β2-AR was situated in membrane or cytoplasm of HemEC andnormal skin vascular endothelial cells, mainly in cytoplasm. Strongly positiveexpression in proliferative stage of hemangioma, positive or weakly positive ininvoluting stage, with significance between these two stages(P<0.05).2. Therewere significant difference of VEGF and VEGFR-2expression in allgroups(P<0.05). But there were weakly positive or negative in vascularmalformations and normal skins, without significance (P>0.05). Positiveexpression of VEGF and VEGFR-2were situated in membrane or cytoplasm ofHemEC and normal skin vascular endothelial cells, mainly in membrane.Strongly positive expression in proliferative stage of hemangioma, positive orweakly positive in involuting stage,with significance between these twostages(P<0.05).3.The expression of β2-AR, VEGF and VEGFR-2wascorrelated in hemangioma. The positive expression between β2-AR and VEGF,β2-AR and VEGFR-2, VEGF and VEGFR-2were significantly positive correlation respectively (“r” was0.539,0.541,0.608, P<0.05).Conclusion:1.β2-AR is strongly positive expression in proliferating stage ofhemangioma, positive or weakly positive expression in involuting stage, nosignificant expression in vascular malformation and normal skin. But β1andβ3-AR are no significant expression in all groups. This suggested that thepathogenesis of hemangioma may have a certain relationship with theexpression of β2-AR. The expression of β2-AR was significantly higher inproliferative stage than that in involuting stage, suggesting that the lowerexpression of β2-AR may be associated with proliferation changing toinvoluting stage.2. VEGF and VEGFR-2were high expression in proliferatingstage, low expression in involuting stage, no statistically expression in vascularmalformation and normal skin. This suggested that high expression of VEGFattract VEGFR-2clustering and integrating partly, and improve HemECproliferation, migration, differentiation and angiogenesis.3. The positivecorrelation of β2-AR, VEGF and VEGF-2in proliferating hemangiomasuggested that β2-AR may affect the expression of VEGF in HemEC, andtransactivate VEGFR-2signaling and further increase HemEC proliferation.