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Original Investigation
October 13, 2016

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

Author Affiliations
  • 1Division of Pediatric Otolaryngology and Center for the Investigation of Congenital Aberrancies of Vascular Development, Department of Otolaryngology–Head and Neck Surgery, University of Arkansas for the Medical Sciences, Little Rock
  • 2Department of Otolaryngology Head and Neck Surgery, Arkansas Children’s Hospital, Little Rock
JAMA Facial Plast Surg. Published online October 13, 2016. doi:10.1001/jamafacial.2016.1188
Key Points

Question  What is the relative β-adrenergic receptor subtype expression profile for infantile hemangioma in proliferation, involution, and response to propranolol treatment?

Findings  In this case-control study of 33 specimens of infantile hemangioma, the level of ADBR1 messenger RNA and protein expression was higher in proliferative hemangioma. Protein expression of ADBR3 was greater in involuted and propranolol-responsive hemangiomas.

Meaning  These data demonstrate a variable β-adrenergic receptor expression profile for infantile hemangioma in various stages, providing insight into pathogenesis and potential treatment options.

Abstract

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 β1-, β2-, and β3-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 specimens were 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 by Western 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 β-blockade.

Level of Evidence  2.

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