Protective role of CXCR7 activation in neonatal hyperoxia-induced systemic vascular remodeling and cardiovascular dysfunction in juvenile rats

Protective role of CXCR7 activation in neonatal hyperoxia-induced systemic vascular remodeling and cardiovascular dysfunction in juvenile rats

Neonatal hyperoxia induces long-term systemic vascular stiffness and cardiovascular remodeling, but the mechanisms are unclear. Chemokine receptor 7 (CXCR7) represents a key regulator of vascular homeostasis and repair by modulating TGF-β1 signaling. This study investigated whether pharmacological C...

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Bibliographic Details
Published in:Scientific reports Vol. 13; no. 1; p. 19538
Main Authors: Benny, Merline, Sharma, Mayank, Kulandavelu, Shathiyah, Chen, PingPing, Tian, Runxia, Ballengee, Sydne, Huang, Jiang, Levine, Amanda F., Claure, Matteo, Schmidt, Augusto F., Vazquez-Padron, Roberto I., Rodrigues, Claudia O., Wu, Shu, Velazquez, Omaida C., Young, Karen C.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 09-11-2023
Nature Publishing Group
Nature Portfolio
Subjects:
631/443/592/75/593/2724
692/4019/592/75/230
Animals
Animals, Newborn
Aorta
Chemokine receptors
Coronary artery
Doppler effect
Echocardiography
Endothelial Cells
Fibrosis
Homeostasis
Humanities and Social Sciences
Humans
Hyperoxia
Hyperoxia - complications
Juveniles
multidisciplinary
Neonates
Pulse Wave Analysis
Rats
Rats, Sprague-Dawley
Science
Science (multidisciplinary)
Transforming Growth Factor beta1
Transforming growth factor-b1
Vascular Remodeling
Ventricle
Ventricular Dysfunction, Left
Wave velocity
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Summary:Neonatal hyperoxia induces long-term systemic vascular stiffness and cardiovascular remodeling, but the mechanisms are unclear. Chemokine receptor 7 (CXCR7) represents a key regulator of vascular homeostasis and repair by modulating TGF-β1 signaling. This study investigated whether pharmacological CXCR7 agonism prevents neonatal hyperoxia-induced systemic vascular stiffness and cardiac dysfunction in juvenile rats. Newborn Sprague Dawley rat pups assigned to room air or hyperoxia (85% oxygen), received CXCR7 agonist, TC14012 or placebo for 3 weeks. These rat pups were maintained in room air until 6 weeks when aortic pulse wave velocity doppler, cardiac echocardiography, aortic and left ventricular (LV) fibrosis were assessed. Neonatal hyperoxia induced systemic vascular stiffness and cardiac dysfunction in 6-week-old rats. This was associated with decreased aortic and LV CXCR7 expression. Early treatment with TC14012, partially protected against neonatal hyperoxia-induced systemic vascular stiffness and improved LV dysfunction and fibrosis in juvenile rats by decreasing TGF-β1 expression. In vitro, hyperoxia-exposed human umbilical arterial endothelial cells and coronary artery endothelial cells had increased TGF-β1 levels. However, treatment with TC14012 significantly reduced the TGF-β1 levels. These results suggest that dysregulation of endothelial CXCR7 signaling may contribute to neonatal hyperoxia-induced systemic vascular stiffness and cardiac dysfunction.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-46422-3