title: Antagonism of CXCR7 attenuates chronic hypoxia-induced pulmonary hypertension.
abstract: BACKGROUND
  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 2 wk. After 1 wk 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/LV+S, and pulmonary vascular cell proliferation and remodeling, the administration of CCX771 markedly decreased these changes.
  
  
  CONCLUSIONS
  These results indicate that antagonism of CXCR7 may be a potent strategy to decrease PH and vascular remodeling.
authors.affiliation: Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Ecaterina
authors.initials: E
authors.lastname: Sartina
authors.forename: Cleide
authors.initials: C
authors.lastname: Suguihara
authors.forename: Shalini
authors.initials: S
authors.lastname: Ramchandran
authors.forename: Patrick
authors.initials: P
authors.lastname: Nwajei
authors.forename: Myra
authors.initials: M
authors.lastname: Rodriguez
authors.forename: Eneida
authors.initials: E
authors.lastname: Torres
authors.forename: Dorothy
authors.initials: D
authors.lastname: Hehre
authors.forename: Carlos
authors.initials: C
authors.lastname: Devia
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Walters
authors.forename: Mark E T
authors.initials: ME
authors.lastname: Penfold
authors.forename: Karen C
authors.initials: KC
authors.lastname: Young
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001158:Arteries / Q000187:drug effects / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D000860:Hypoxia / Q000150:complications*; D008168:Lung / Q000098:blood supply / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D011247:Pregnancy; D054387:Receptors, CXCR / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism
chemical_list: C501897:Cmkor1 protein, mouse; D054387:Receptors, CXCR