The Patent Ductus Arteriosus in Extremely Preterm Neonates Is More than a Hemodynamic Challenge: New Molecular Insights

Anna Sellmer, Tine Brink Henriksen, Johan Palmfeldt, Bodil Hammer Bech, Julie Astono, Tue Bjerg Bennike, Vibeke Elisabeth Hjortdal

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

Complications to preterm birth are numerous, including the presence of a patent ductus arteriosus (PDA). The biological understanding of the PDA is sparse and treatment remains controversial. Herein, we speculate whether the PDA is more than a cardiovascular imbalance, and may be a marker in response to immature core molecular and physiological processes driven by biological systems, such as inflammation. To achieve a new biological understanding of the PDA, we performed echocardiography and collected plasma samples on day 3 of life in 53 consecutively born neonates with a gestational age at birth below 28 completed weeks. The proteome of these samples was analyzed by mass spectrometry (nanoLC-MS/MS) and immunoassay of 17 cytokines and chemokines. We found differences in 21 proteins and 8 cytokines between neonates with a large PDA (>1.5 mm) compared to neonates without a PDA. Amongst others, we found increased levels of angiotensinogen, periostin, pro-inflammatory associations, including interleukin (IL)-1β and IL-8, and anti-inflammatory associations, including IL-1RA and IL-10. Levels of complement factors C8 and carboxypeptidases were decreased. Our findings associate the PDA with the renin-angiotensin-aldosterone system and immune- and complement systems, indicating that PDA goes beyond the persistence of a fetal circulatory connection of the great vessels.

Original languageEnglish
Article number1179
JournalBiomolecules
Volume12
Issue9
Number of pages16
DOIs
Publication statusPublished - Sept 2022

Keywords

  • angiotensinogen
  • inflammation
  • patent ductus arteriosus
  • periostin
  • preterm neonate
  • proteomics
  • Premature Birth
  • Interleukin-10
  • Humans
  • Proteome
  • Interleukin-8
  • Tandem Mass Spectrometry
  • Angiotensinogen
  • Female
  • Infant, Extremely Premature
  • Interleukin 1 Receptor Antagonist Protein
  • Ductus Arteriosus, Patent/complications
  • Hemodynamics
  • Infant, Newborn

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