title: SDF-1α upregulation by atorvastatin in rats with acute myocardial infarction via nitric oxide production confers anti-inflammatory and anti-apoptotic effects.
abstract: BACKGROUND
  The effects of atorvastatin on SDF-1α expression under acute myocardial infarction (AMI) are still unclear. Therefore, our present study is to investigate the roles and mechanisms of atorvastatin treatment on SDF-1α expression in rats with AMI.
  
  
  METHODS
  Male Sprague-Dawley rats were underwent permanent coronary artery ligation and randomly assigned into four groups as follow: blank control (B), atorvastatin (A), atorvastatin plus L-NAME (A+L-NAME), and atorvastatin plus AMD3100 (A+AMD3100). Rats underwent similar procedure but without ligation were used as group sham operated (S). Atorvastatin (10mg/Kg/d body weight) was administrated by gavage to rats in three atorvastatin treated groups, and L-NAME (40 mg/Kg/d body weight) or AMD3100 (5mg/Kg/d body weight) was given to group A+L-NAME or A+AMD3100, respectively.
  
  
  RESULTS
  Comparing with group B, NO production, SDF-1α and CXCR4 expression were significantly up-regulated in three atorvastatin treated groups at the seventh day. However, the increments of SDF-1α and CXCR4 expression in group A+L-NAME were reduced when NO production was inhibited by L-NAME. Anti-inflammatory and anti-apoptotic effects of atorvastatin were offset either by decrease of SDF-1α and CXCR4 expression (by L-NAME) or blockage of SDF-1α coupling with CXCR4 (by AMD3100). Expression of STAT3, a cardioprotective factor mediating SDF-1α/CXCR4 axis induced cardiac protection, was up-regulated most significantly in group A. The effects of atorvastatin therapy on cardiac function were also abrogated either when SDF-1α and CXCR4 expression was diminished or the coupling of SDF-1α with CXCR4 was blocked.
  
  
  CONCLUSIONS
  SDF-1α upregulation by atorvastatin in rats with AMI was, at least partially, via the eNOS/NO dependent pathway, and SDF-1α upregulation and SDF-1α coupling with CXCR4 conferred anti-inflammatory and anti-apoptotic effects under AMI setting which we speculated that ultimately contributed to cardiac function improvement.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China.
authors.forename: Ruofeng
authors.initials: R
authors.lastname: Qiu
authors.forename: Anping
authors.initials: A
authors.lastname: Cai
authors.forename: Yugang
authors.initials: Y
authors.lastname: Dong
authors.forename: Yingling
authors.initials: Y
authors.lastname: Zhou
authors.forename: Danqing
authors.initials: D
authors.lastname: Yu
authors.forename: Yuli
authors.initials: Y
authors.lastname: Huang
authors.forename: Dongdan
authors.initials: D
authors.lastname: Zheng
authors.forename: Shaoqi
authors.initials: S
authors.lastname: Rao
authors.forename: Yingqing
authors.initials: Y
authors.lastname: Feng
authors.forename: Weiyi
authors.initials: W
authors.lastname: Mai
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D000069059:Atorvastatin; D001596:Benzylamines; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D003331:Coronary Vessels / Q000601:surgery; D000080027:Cyclams; D006538:Heptanoic Acids / Q000008:administration & dosage; D006571:Heterocyclic Compounds / Q000008:administration & dosage; D008026:Ligation / Q000379:methods; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism; D011758:Pyrroles / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D001596:Benzylamines; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D000080027:Cyclams; D006538:Heptanoic Acids; D006571:Heterocyclic Compounds; D011758:Pyrroles; D019718:Receptors, CXCR4; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D009569:Nitric Oxide; D000069059:Atorvastatin; C088327:plerixafor; D019331:NG-Nitroarginine Methyl Ester