title: Role for granulocyte colony stimulating factor in angiotensin II-induced neutrophil recruitment and cardiac fibrosis in mice.
abstract: BACKGROUND
  Granulocyte colony stimulating factor (G-CSF) is a key mediator of neutrophil infiltration and is profibrotic in the liver, lung, and infarcted heart, but its roles in angiotensin II (Ang II)-induced hypertension and cardiac remodeling have not been fully determined. Thus, we sought to investigate the causal relation of G-CSF to neutrophil recruitment and cardiac fibrosis in C57BL/6J mice.
  
  
  METHODS
  Hypertension and cardiac fibrosis were induced in wild-type (WT) mice receiving continuous infusion of Ang II (1,500ng/kg/min). After 7 days, heart sections were stained with hematoxylin and eosin, Masson's trichrome, and immunohistochemistry. The mRNA expression of cytokines was detected by real-time polymerase chain reaction analysis. The protein levels were measured by Western blot analysis.
  
  
  RESULTS
  After Ang II infusion, myocardial G-CSF expression was significantly elevated in the hearts. Moreover, WT mice exhibited increased blood pressure, marked neutrophil accumulation, proinflammatory cytokine expression, reactive oxygen species production, and cardiac fibrosis after 7 days of Ang II infusion. However, administration of anti-G-CSF neutralizing antibody, but not with control immunoglobulin G, significantly attenuated these effects. In addition, neutralizing G-CSF antibody reversed Ang II-induced activation of ERK1/2, STAT3, and AKT signaling pathways in the hearts.
  
  
  CONCLUSIONS
  This study demonstrates that G-CSF plays a critical role in hypertension and cardiac fibrosis and targeting this cytokine may be a novel therapeutic strategy to ameliorate hypertensive heart disease.
authors.affiliation: Key Laboratory of Remodeling-Related Cardiovascular Diseases, Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Ministry of Education, Beijing, China.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Jiang
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: Zeng
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Li
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D005355:Fibrosis; D005979:Glutathione Peroxidase / Q000096:biosynthesis; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology*; D020556:Neutrophil Infiltration / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000187:drug effects; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000906:Antibodies; D016207:Cytokines; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D000804:Angiotensin II; D016179:Granulocyte Colony-Stimulating Factor; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D051057:Proto-Oncogene Proteins c-akt; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse
keywords: angiotensin II; blood pressure; cardiac fibrosis; granulocyte colony stimulating factor; hypertension; neutrophils.