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 β 1 - and β 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 β 1 -, β 2 -, and β 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 β 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 β 2 -adrenoceptor mRNA. In LM, the expression of β 2 -adrenoceptor mRNA was ninefold higher than that of β 1 -adrenoceptor mRNA. VM showed low expression levels of all β-adrenoceptor mRNAs, and β 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 β-adrenoceptor subtype mRNA levels.