Expression and Correlation Analysis of β-adrenoceptors, VEGF, MMP-9 and Caspase-3 in Different Phases of Infantile Hemangioma

Objective: To investigate the expression and correlation analysis of beta-adrenoceptors (AR), VEGF, MMP-9 and caspase-3 in the different phases of infantile hemangioma (IH) and to find out the possible mechanism of beta-AR antagonist propranolol treatment for IH. Methods: 52 fresh operative IH specimens were collected and were divided into 2 groups: 32 patients of proliferating phase and 20 patients of involuting phase. Ten specimens of normal skin were also collected as the control group. The expression of beta-AR, VEGF, MMP-9 and caspase-3 were detected by immunohistochemistry. The integral optical density and positive area rate of beta-AR, VEGF, MMP-9 and caspase-3 were examined using a microscopic image analysis system. The correlations among the above markers were also analyzed using Pearson correlation coefficients. Results: beta 1-AR and beta 2-AR were both strongly expressed in the proliferating and involuting hemangioma tissue. There was a significant difference (P<0.01) for the expression of beta 1-AR and beta 2-AR between the hemangioma tissue and the normal skin. VEGF and MMP-9 were strongly expressed in the proliferating hemangioma and weakly expressed in the involuting hemangioma, and there was a significant difference (P<0.01) for the expression of VEGF and MMP-9 between the proliferating hemangioma and involuting hemangioma or between the proliferating hemangioma and the normal skin. There was a significantly positive correlation between the expression of beta-AR and the expression of VEGF and MMP-9 in the proliferating phase of IH. There was a significant difference (P<0.01) for the expression of caspase-3 between the proliferating hemangioma and involuting hemangioma or between the involuting hemangioma and the normal skin. There was a significantly negative correlation between the expression of beta-AR, VEGF and MMP-9 and the expression of caspase-3 in the proliferating phase of IH. Conclusions: beta-AR, VEGF, MMP-9 and caspase-3 have an effect on the pathogenesis of hemangioma. beta-AR antagonist propranolol might treat IH by the mechanism of regulating the beta-AR/VEGF/MMP-9/caspase-3 pathway, inhibit the proliferation of hemangioma, promote the apoptosis of hemangioma, and eventually bring about the regression of IH.