title: Deficiency of the NHE1 gene prevents hypoxia-induced pulmonary hypertension and vascular remodeling.
abstract: BACKGROUND
  Our previous studies found that Na(+)/H(+) exchanger (NHE) activity played an essential role in pulmonary artery smooth muscle cell (PASMC) proliferation and in the development of hypoxia-induced pulmonary hypertension and vascular remodeling. Other investigators recently observed increased expression of the NHE isoform 1 (NHE1) gene in rodents with pulmonary hypertension induced by hypoxia. However, a causal role for the NHE1 gene in pulmonary hypertension has not been determined.
  
  
  OBJECTIVE
  To determine the causal role of the NHE1 gene in pulmonary hypertension and vascular remodeling.
  
  
  METHODS
  We used NHE1-null mice to define the role of the NHE1 gene in the development of pulmonary hypertension and remodeling induced by hypoxia and to delineate the NHE1 regulatory pathway.
  
  
  RESULTS
  After 2 weeks of exposure to hypoxia, in contrast to wild-type hypoxic littermates, there was no significant increase in right ventricular systolic pressure, in the ratio of right ventricular to left ventricular plus septal weight [RV/(LV + S)], or in medial wall thickness of the pulmonary arterioles in homozygous mice (NHE1(-/-)). There was a significant decrease in Rho kinase (ROCK1 and ROCK2) expression, accompanied by an increase in p27 expression in NHE1(-/-) mice.
  
  
  CONCLUSIONS
  Our study demonstrated that deficiency of the NHE1 gene prevented the development of hypoxia-induced pulmonary hypertension and vascular remodeling in mice and revealed a novel regulatory pathway associated with NHE1 signaling.
authors.affiliation: Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Bulfinch-148, Boston, MA 02114-2696, USA.
authors.forename: Lunyin
authors.initials: L
authors.lastname: Yu
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Quinn
authors.forename: Hari G
authors.initials: HG
authors.lastname: Garg
authors.forename: Charles A
authors.initials: CA
authors.lastname: Hales
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000172:deficiency* / Q000235:genetics*; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D000860:Hypoxia; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics*; D014655:Vascular Resistance / Q000502:physiology; D017725:Ventricular Pressure / Q000502:physiology; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C490997:Slc9a1 protein, mouse; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D054460:rho-Associated Kinases