title: The ontogeny of human pulmonary angiotensin-converting enzyme and its aberrant expression may contribute to the pathobiology of bronchopulmonary dysplasia (BPD).
abstract: BACKGROUND
  The mammalian lung possesses the highest level of angiotensin converting enzyme (ACE) amongst all the organs. ACE is known to generate angiotensin (AT)-II from AT-I and to regulate serum bradykinin level, thereby controlling blood pressure. Recent data, however, indicate a role for ACE derived AT-II in angiogenesis, pulmonary hypertension, and neonatal lung disease. The ontogeny of ACE in humans has not been investigated. We studied pulmonary ACE expression during human lung development and in human bronchopulmonary dysplasia (BPD).
  
  
  METHODS
  Human fetal autopsy lung tissue representing all three trimesters (12, 13, 16, 18, 24, 34, 39, and 40 weeks of gestational age (WGA)), as well as from 1 to 10 years of age with no significant lung pathology were used. In addition lung sections of patients with BPD (n = 5) were selected. The slides were immunostained using an anti-ACE monoclonal antibody. The temporal and spatial pattern of ACE expression was contrasted to that of the pan-endothelial marker CD31. Staining intensity was graded.
  
  
  RESULTS
  Mildly diffuse and strong microvascular endothelial immunreactivity for ACE was seen in the human fetus as early as 12 WGA. ACE expression peaked at mid gestation and remained high throughout gestation and postnatally. In BPD lungs ACE endothelial staining was largely absent, and when focal staining was observed the intensity was weak.
  
  
  CONCLUSIONS
  We established that ACE expression is present in the human fetal lung as early as 12 WGA, remains active pre- and postnatally, and ACE expression was downregulated in BPD lungs. We speculate that ACE may be involved in the process of lung development.
authors.affiliation: Department of Pathology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
authors.forename: E C
authors.initials: EC
authors.lastname: Castro
authors.forename: W T
authors.initials: WT
authors.lastname: Parks
authors.forename: C
authors.initials: C
authors.lastname: Galambos
mesh_terms: D000818:Animals; D001997:Bronchopulmonary Dysplasia / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D004727:Endothelium / Q000378:metabolism; D005260:Female; D005333:Fetus; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008168:Lung / Q000196:embryology / Q000201:enzymology* / Q000473:pathology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D013194:Staining and Labeling
chemical_list: D007703:Peptidyl-Dipeptidase A
keywords: angiotensin-converting enzyme; bronchopulmonary dysplasia; development; lung