title: Decreased eNOS protein expression in involuting and propranolol-treated hemangiomas.
abstract: OBJECTIVE
  To examine the location and degree of endothelial nitric oxide synthase (eNOS) protein expression in hemangioma growth, involution, and during propranolol therapy.
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Pediatric patients with hemangiomas.
  
  
  METHODS
  Fresh human hemangioma specimens at various stages of development were harvested. Effective propranolol therapy had been implemented in some patients. Quantitative assessment and localization of eNOS protein expression was performed on each specimen by Western blot analysis and immunohistochemical analysis, respectively.
  
  
  RESULTS
  Hemangiomas in a proliferative phase (group 1: n = 4; mean [SD] age, 4.25 [2.06] months), an early involuting phase (group 2: n = 6; 12.00 [1.64] months), and a late involuting phase (group 3: n = 6; 23.30 [1.97] months) were harvested. The mean (SD) eNOS protein expression was 0.88 (0.41) in group 1, 0.26 (0.26) in group 2, and 0.15 (0.08) in group 3, respectively. A statistically significant decrease in eNOS protein expression was observed between proliferating and involuting hemangiomas (group 1 vs group 2 and group 3; P ≤ .01) but not between early and late phases of involution (P = .17). In a separate propranolol treatment group (n = 7), the eNOS protein level was significantly lower than in age-matched controls (n = 7; 0.08 [0.1] vs 0.45 [0.45]; P = .03). Immunohistochemical analysis demonstrated eNOS to be predominately in endothelial cells lining mature blood vessels.
  
  
  CONCLUSIONS
  Expression of eNOS protein decreases during the hemangioma lifecycle. Propranolol may suppress hemangioma growth by inhibiting expression of eNOS protein and subsequent production of nitric oxide.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Division of Pediatric Otolaryngology and Center for the Investigation of Congenital Aberrancies of Vascular Development, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, 1 Children's Way, Little Rock, AR 72207, USA.
authors.forename: Yuemeng
authors.initials: Y
authors.lastname: Dai
authors.forename: Fang
authors.initials: F
authors.lastname: Hou
authors.forename: Lisa
authors.initials: L
authors.lastname: Buckmiller
authors.forename: Chun-Yang
authors.initials: CY
authors.lastname: Fan
authors.forename: Ali
authors.initials: A
authors.lastname: Saad
authors.forename: James
authors.initials: J
authors.lastname: Suen
authors.forename: Gresham T
authors.initials: GT
authors.lastname: Richter
mesh_terms: D000293:Adolescent; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006391:Hemangioma / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007223:Infant; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D011433:Propranolol / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D011433:Propranolol; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III