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American Heart Association

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Final ID: Su4178

Opposing Responses to Oxygen in the Rabbit Ductus Arteriosus and Fetal Pulmonary Arteries: Proteomic Analysis Reveals Significant Metabolic Differences

Abstract Body (Do not enter title and authors here): Introduction: The ductus arteriosus (DA) is a fetal vessel connecting the pulmonary artery (PA) and aorta, diverting oxygenated blood away from the developing lungs to the systemic circulation. Following the first breath, the DA rapidly constricts in response to increased arterial oxygen (O2) which simultaneously induces relaxation of small resistance pulmonary arteries (rPA). These changes, vital for adaptation to neonatal life, separate the pulmonary and systemic circulations (DA vasoconstriction) and enable adequate perfusion of newly ventilated lungs (PA vasodilation). The underlying mechanism of these opposite O2 responses is not fully understood. A failure of either vessel to appropriately respond to O2 results in clinical complications, notably persistent ductus arteriosus or persistent pulmonary hypertension of the newborn. To examine the underlying differences in these fetal vessels, we performed proteomics on fetal rabbit DA and rPA.
Methods: DA and rPA were isolated from male (n=4) and female (n=4) term (30 days gestation) fetal New Zealand white rabbits (protocol #2021-2122). Extracted protein was labelled with TMTpro mass tag labeling. Following HPLC fractionation, samples were run on the ThermoFisher Orbitrap Eclipse Mass Spectrometer. Analysis was completed using ThermoFisher Proteome Discoverer software and DESeq2.
Results: There were 3103 significantly, differentially expressed proteins between the DA and PA(Benjamini Hochberg adjusted p<0.05), 232 of which were ±1.5-fold differentially expressed (Figure 1). Using KEGG pathway analysis the most significantly DA enriched pathway is “Starch and sucrose metabolism” (map00500) and the most significantly rPA enriched pathway is “Sulfur Metabolism” (map00920). There was also rPA enrichment of other metabolic pathways including “Fatty Acid Degradation” (map00071), “Pyruvate Metabolism” (map00620), and “Glycolysis/Gluconeogenesis” (map00010).
Conclusions: This analysis reveals unique mitochondrial metabolic pathways that may contribute to the opposing tissue responses of these specialized blood vessels to O2. Exploration of these pathways may identify potential therapeutic targets and inform future investigations of differential O2 sensing in DA and rPA.
  • Bentley, Rachel  ( Queen's University , Kingston , Ontario , Canada )
  • Prins, Kurt  ( University of Minnesota , Minneapolis , Minnesota , United States )
  • Martin, Ashley  ( Queen's University , Kingston , Ontario , Canada )
  • Emon, Isaac  ( Queen's University , Kingston , Ontario , Canada )
  • Hindmarch, Charles  ( Queen's University , Kingston , Ontario , Canada )
  • Archer, Stephen  ( Queens University , Kingston , Ontario , Canada )
  • Author Disclosures:
    Rachel Bentley: DO NOT have relevant financial relationships | Kurt Prins: DO NOT have relevant financial relationships | Ashley Martin: DO NOT have relevant financial relationships | Isaac Emon: DO NOT have relevant financial relationships | Charles Hindmarch: DO NOT have relevant financial relationships | Stephen Archer: DO NOT have relevant financial relationships
Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

When Cells and Molecules Go Bad: Molecular Mechanisms of Pulmonary Vascular Disease

Sunday, 11/17/2024 , 03:15PM - 04:15PM

Abstract Poster Session

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