ß1-Adrenoceptor mRNA level reveals distinctions between infantile hemangioma and vascular malformations.

ABSTRACT

BACKGROUND: Infantile hemangioma (IH) is the most frequent vascular tumor of early childhood. Recently, propranolol, a nonselective ß1- and ß2-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 ß1-, ß2-, and ß3-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 ß1-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 ß2-adrenoceptor mRNA. In LM, the expression of ß2-adrenoceptor mRNA was ninefold higher than that of ß1-adrenoceptor mRNA. VM showed low expression levels of all ß-adrenoceptor mRNAs, and ß3-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 ß-adrenoceptor subtype mRNA levels.