title: The expression of renin-angiotensin-aldosterone axis components in infantile hemangioma tissue and the impact of propranolol treatment.
abstract: BackgroundPropranolol's mechanism of action for controlling infantile hemangioma (IH) remains unclear. We hypothesize that this nonselective beta antagonist downregulates renin-angiotensin-aldosterone (RAA) axis components, preventing angiogenic substrate induction of IH.MethodsIH tissue and serum were collected from children with propranolol-treated or -untreated IH during surgery. Normal skin and serum from demographically matched children were used as controls. Real-time PCR 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 enzyme-linked immunosorbent assay (ELISA).ResultsThere were significantly greater messenger RNA (mRNA) levels of angiotensinogen (AGT) in proliferating IH, but not in involuting or treated IH, when compared with controls (P<0.05). Angiotensin-converting enzyme (ACE) and angiotensin II receptor 1 (AGTR1) mRNA expression was higher in all IH specimens when comparedwith controls (P<0.05). ACE and AGTR1 protein expression was greater in proliferating IH tissue compared with that in controls and in involuting and treated IH tissue (P<0.05). ELISA showed no significant difference in ACE serum levels but did show a significant reduction in renin in involuting compared with proliferating IH (P<0.05).ConclusionsThe protein and mRNA expression of several RAA pathway constituents is elevated in IH tissue when compared with that in normal tissue. The action of propranolol on IH may be the result of reductions in ACE and AGTR1.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: James R
authors.initials: JR
authors.lastname: Dornhoffer
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Ting
authors.initials: T
authors.lastname: Wei
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Haihong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Emily
authors.initials: E
authors.lastname: Miller
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Mario
authors.initials: M
authors.lastname: A Cleves
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Gresham T
authors.initials: GT
authors.lastname: Richter
mesh_terms: D000808:Angiotensinogen / Q000378:metabolism; D049109:Cell Proliferation; D002675:Child, Preschool; D005260:Female; D018324:Hemangioma, Capillary / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008099:Liver / Q000378:metabolism; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011433:Propranolol / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System; D012867:Skin / Q000378:metabolism
chemical_list: C544065:AGTR1 protein, human; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D011433:Propranolol; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A