Antagonism of CXCR7 attenuates chronic hypoxia-induced pulmonary hypertension

Ecaterina Sartina, Cleide Suguihara, Shalini Ramchandran, Patrick Nwajei, Myra Rodriguez, Eneida Torres, Dorothy Hehre, Carlos Devia, Matthew J. Walters, Mark E T Penfold, Karen Young

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Introduction: Chemokines may directly participate in the pathogenesis of neonatal chronic hypoxia-induced pulmonary hypertension (PH). Although stromal-derived factor-1 (SDF-1) has been shown to be involved in PH, the role of its most recently discovered receptor, chemokine receptor type 7 (CXCR7), remains unclear. We sought to determine whether antagonism of the CXCR7 receptor would decrease pulmonary vascular remodeling in newborn mice exposed to chronic hypoxia by decreasing pulmonary vascular cell proliferation. Methods: Neonatal mice were exposed to hypoxia (fractional inspired oxygen concentration = 0.12) or room air (RA) for 2wk. After 1wk of exposure, mice received daily injections of placebo or a CXCR7 antagonist (CCX771) from postnatal day 7 (P7) to P14. Right ventricular systolic pressure (RVSP), the ratio of the weight of the right ventricle to left ventricle septum (RV/LV S), and pulmonary vascular cell proliferation and remodeling were determined at P14. Results: As compared with mice exposed to RA, hypoxia placebo mice had a significant increase in the lung protein expression of CXCR7. Although hypoxic placebo-treated mice had a significant increase in RVSP, RV/LVS, and pulmonary vascular cell proliferation and remodeling, the administration of CCX771 markedly decreased these changes. Discussion: These results indicate that antagonism of CXCR7 may be a potent strategy to decrease PH and vascular remodeling.

Original languageEnglish
Pages (from-to)682-688
Number of pages7
JournalPediatric Research
Volume71
Issue number6
DOIs
StatePublished - Jun 1 2012

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Pulmonary Hypertension
Lung
Blood Vessels
Placebos
Cell Proliferation
Ventricular Pressure
Heart Ventricles
Air
Blood Pressure
Chemokine Receptors
Chemokines
Hypoxia
Oxygen
Weights and Measures
Injections
Proteins

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Sartina, E., Suguihara, C., Ramchandran, S., Nwajei, P., Rodriguez, M., Torres, E., ... Young, K. (2012). Antagonism of CXCR7 attenuates chronic hypoxia-induced pulmonary hypertension. Pediatric Research, 71(6), 682-688. https://doi.org/10.1038/pr.2012.30

Antagonism of CXCR7 attenuates chronic hypoxia-induced pulmonary hypertension. / Sartina, Ecaterina; Suguihara, Cleide; Ramchandran, Shalini; Nwajei, Patrick; Rodriguez, Myra; Torres, Eneida; Hehre, Dorothy; Devia, Carlos; Walters, Matthew J.; Penfold, Mark E T; Young, Karen.

In: Pediatric Research, Vol. 71, No. 6, 01.06.2012, p. 682-688.

Research output: Contribution to journalArticle

Sartina, E, Suguihara, C, Ramchandran, S, Nwajei, P, Rodriguez, M, Torres, E, Hehre, D, Devia, C, Walters, MJ, Penfold, MET & Young, K 2012, 'Antagonism of CXCR7 attenuates chronic hypoxia-induced pulmonary hypertension', Pediatric Research, vol. 71, no. 6, pp. 682-688. https://doi.org/10.1038/pr.2012.30
Sartina E, Suguihara C, Ramchandran S, Nwajei P, Rodriguez M, Torres E et al. Antagonism of CXCR7 attenuates chronic hypoxia-induced pulmonary hypertension. Pediatric Research. 2012 Jun 1;71(6):682-688. https://doi.org/10.1038/pr.2012.30
Sartina, Ecaterina ; Suguihara, Cleide ; Ramchandran, Shalini ; Nwajei, Patrick ; Rodriguez, Myra ; Torres, Eneida ; Hehre, Dorothy ; Devia, Carlos ; Walters, Matthew J. ; Penfold, Mark E T ; Young, Karen. / Antagonism of CXCR7 attenuates chronic hypoxia-induced pulmonary hypertension. In: Pediatric Research. 2012 ; Vol. 71, No. 6. pp. 682-688.
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