Expression of β-Adrenergic Receptor Subtypes in Proliferative, Involuted, and Propranolol-Responsive Infantile Hemangiomas

IMPORTANCE Propranolol hydrochloride has become the primary medical treatment for problematic infantile hemangioma; however, the expression of propranolol's target receptors during growth, involution, and treatment of hemangioma remains unclear. OBJECTIVE To measure and compare the expression of beta 1-, beta 2-, and beta 3-adrenergic receptors (ADBR1, ADBR2, and ADBR3, respectively) in proliferative (n = 10), involuted (n = 11), and propranolol-responsive (n = 12) hemangioma tissue. DESIGN, SETTING, AND PARTICIPANTS Infantile hemangioma specimenswere harvested for molecular investigation. Messenger RNA (mRNA) expression of the ADBR1, ADBR2, and ADBR3 genes was detected by real-time polymerase chain reaction. Protein level expression was measured byWestern blot and standardized with densitometry. A total of 33 specimens were collected from patients in a tertiary pediatric hospital who underwent excision of problematic hemangiomas. This study was conducted from January 18, 2011, to September 24, 2013, and data analysis was performed from February 25, 2015, to June 25, 2016. RESULTS Of the 33 patients included, 21 were female (64%). The mean (SD) patient age at the time of excision was 7 (2.5) months for the proliferative group lesions, 23.5 (10) months for the involuted group, and 16 (10) months for the propranolol group. The mean level of ADBR1 mRNA expression was significantly higher in proliferative hemangioma than in propranolol-responsive hemangioma (1.05 [0.56] vs 0.52 [0.36]; P =.01; 95% CI, 0.12-0.94). There was no difference in ADBR2 expression among the groups. Protein expression of ADBR3 was significantly higher in involuted (0.64 [0.12] vs 0.26 [0.04]; P < .01; 95% CI, 0.26-0.49) and propranolol-responsive hemangioma (0.66 [0.31] vs 0.26 [0.04]; P =.01; 95% CI, 0.16-0.68) compared with proliferative hemangioma. CONCLUSIONS AND RELEVANCE These data demonstrate the variable expression of ADBR subtypes among infantile hemangiomas during growth, involution, and response to treatment. These findings may have clinical implications regarding the use of selective vs nonselective a-blockade.