The expression of renin-angiotensin-aldosterone axis components in infantile hemangioma tissue and the impact of propranolol treatment.
Pediatr Res. 2017 Apr 04;:
Authors: Dornhoffer JR, Wei T, Zhang H, Miller E, Cleves M, Richter GT
Abstract
BACKGROUND: Propranolol's mechanism of action for controlling infantile hemangioma (IH) remains unclear. We hypothesize that this non-selective beta antagonist downregulates Renin-Angiotensin-Aldosterone (RAA) axis components, preventing angiogenic substrate induction of IH.
METHODS: IH tissue and serum were collected from children with propranolol-treated or untreated IHs during surgery. Patients' normal skin and serum from demographically matched children were used as controls. rtPCR and Western blot quantified RAA components in proliferative (n=10), involuting (n=10), propranolol-treated (n=12) IH, and normal specimens (n=11). Serum was analyzed by ELISA.
RESULTS: There were significantly greater mRNA levels of angiotensinogen (AGT) in proliferating, but not involuting or treated IH, versus controls (P<0.05). Angiotensin converting enzyme (ACE) and angiotensin II receptor 1 (AGTR1) mRNA expression was higher in all IH specimens versus controls (P<0.05). ACE and AGTR1 protein expression was greater in proliferating IH tissue compared to controls and involuting and treated IH (P<0.05). ELISA showed no significant difference in ACE serum levels but did show a significant reduction in renin in involuting versus proliferating IH (P<0.05).
CONCLUSIONS: Protein and mRNA expression of several RAA pathway constituents are elevated in IH versus normal tissue. Propranolol's action on IH may be the result of reductions in ACE and AGTR1.Pediatric Research accepted article preview online, 04 April 2017. doi:10.1038/pr.2017.93.
PMID: 28376078 [PubMed - as supplied by publisher]
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