title: Effect of chemokine receptor CXCR4 on hypoxia-induced pulmonary hypertension and vascular remodeling in rats.
abstract: BACKGROUND
  CXCR4 is the receptor for chemokine CXCL12 and reportedly plays an important role in systemic vascular repair and remodeling, but the role of CXCR4 in development of pulmonary hypertension and vascular remodeling has not been fully understood.
  
  
  METHODS
  In this study we investigated the role of CXCR4 in the development of pulmonary hypertension and vascular remodeling by using a CXCR4 inhibitor AMD3100 and by electroporation of CXCR4 shRNA into bone marrow cells and then transplantation of the bone marrow cells into rats.
  
  
  RESULTS
  We found that the CXCR4 inhibitor significantly decreased chronic hypoxia-induced pulmonary hypertension and vascular remodeling in rats and, most importantly, we found that the rats that were transplanted with the bone marrow cells electroporated with CXCR4 shRNA had significantly lower mean pulmonary pressure (mPAP), ratio of right ventricular weight to left ventricular plus septal weight (RV/(LV+S)) and wall thickness of pulmonary artery induced by chronic hypoxia as compared with control rats.
  
  
  CONCLUSIONS
  The hypothesis that CXCR4 is critical in hypoxic pulmonary hypertension in rats has been demonstrated. The present study not only has shown an inhibitory effect caused by systemic inhibition of CXCR4 activity on pulmonary hypertension, but more importantly also has revealed that specific inhibition of the CXCR4 in bone marrow cells can reduce pulmonary hypertension and vascular remodeling via decreasing bone marrow derived cell recruitment to the lung in hypoxia. This study suggests a novel therapeutic approach for pulmonary hypertension by inhibiting bone marrow derived cell recruitment.
authors.affiliation: Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. lyu3@partners.org
authors.forename: Lunyin
authors.initials: L
authors.lastname: Yu
authors.forename: Charles A
authors.initials: CA
authors.lastname: Hales
mesh_terms: D000818:Animals; D001596:Benzylamines; D001794:Blood Pressure / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D000080027:Cyclams; D004195:Disease Models, Animal; D018274:Electroporation; D049452:Green Fluorescent Proteins / Q000235:genetics; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D017380:Hypertrophy, Right Ventricular / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control; D000860:Hypoxia / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000187:drug effects / Q000276:immunology; D014162:Transfection
chemical_list: D001596:Benzylamines; C486264:Cxcr4 protein, rat; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D049452:Green Fluorescent Proteins; C088327:plerixafor