β1-Adrenoceptor mRNA level reveals distinctions between infantile hemangioma and vascular malformations

BACKGROUND: Infantile hemangioma (IH) is the most frequent vascular tumor of early childhood. Recently, propranolol, a nonselective beta(1)- and beta(2)-adrenoceptor inhibitor, was introduced into the therapy of severe proliferating IH with excellent results. However, the underlying mechanism of action of propranolol is still unclear. METHODS: We performed immunohistochemistry for cluster of differentiation 31 (CD31), D2-40, glucose transporter-1 (GLUT-1), and Ki67 in order to characterize 21 vascular anomalies (nine IH, seven venous malformations (VMs), and five lymphatic malformations (LMs)). Furthermore, we analyzed the expression of beta(1)-, beta(2)-, and beta(3)-adrenoceptor mRNA in these specimens as well as in hemangioma-derived stem cells by quantitative real-time PCR (qPCR). RESULTS: We show that the expression of beta(1)-adrenoceptor mRNA is 10.7-fold higher in IH independent of the proliferative or regressive phase as well as 2.5-fold higher in hemangioma-derived stem cells as compared with beta(2)-adrenoceptor mRNA. In LM, the expression of beta(2)-adrenoceptor mRNA was ninefold higher than that of beta(1)-adrenoceptor mRNA. VM showed low expression levels of all P-adrenoceptor mRNAs, and beta(3)-adrenoceptor mRNA was hardly detectable in any specimens examined. CONCLUSION: These results provide the first evidence of distinctions between IH and vascular malformations with regard to beta-adrenoceptor subtype mRNA levels.