The ontogeny of human pulmonary angiotensin-converting enzyme and its aberrant expression may contribute to the pathobiology of bronchopulmonary dysplasia (BPD)

E. C. Castro, W. T. Parks, C. Galambos*

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Introduction: 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).

Material and Methods: Human fetal autopsy lung tissue representing all three trimesters (12, 13, 16, 18, 24, 34, 39, and 40 weeks of gestational age (WGA)), aswell as from 1 to 10 years of age with no significant lung pathology were used. In addition lung sections of patients with BPD (n5) 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 panendothelial 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 wasweak.

Conclusion: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.

Original languageEnglish (US)
Pages (from-to)985-990
Number of pages6
JournalPediatric Pulmonology
Volume49
Issue number10
DOIs
StatePublished - Jan 1 2014

Keywords

  • Angiotensin-converting enzyme
  • Bronchopulmonary dysplasia
  • Development
  • Lung

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

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