title: Rosuvastatin changes cytokine expressions in ischemic territory and preserves heart function after acute myocardial infarction in rats.
abstract: OBJECTIVE
  To investigate the mechanism of rosuvastatin in preserving cardiac function after acute myocardial infarction (AMI) in a rat model.
  
  
  METHODS
  Sprague-Dawley rats were randomized to receive either rosuvastatin (5 mg/kg every day) or placebo (0.5% CMC-Na), respectively, by daily gavage from 7 days before AMI. Acute myocardial infarction (AMI) model was induced by left anterior descending coronary artery ligation through a lateral thoracotomy in rats. The expressions of stromal-cell-derived factor 1 (SDF-1), chemokine motif CXC receptor 4 (CXCR-4), vascular endothelial growth factor (VEGF), and intercellular adhesion molecule 1 (ICAM-1) in peri-infarction region and nonischemic region at different time points were determined by the Western blot analysis. Immunohistochemistry analysis was performed on the 28th day after AMI to investigate the accumulation of CD90+, CD133+, and c-kit+ progenitor cells in the peri-infarction region. Masson staining and echocardiograph were performed to evaluate the left ventricular remodeling and postinfarction cardiac function 4 weeks after AMI.
  
  
  RESULTS
  Western blot analysis showed that rosuvastatin could change the cytokine expressions in the peri-infarction region by upregulating the SDF-1 expression and downregulating the expressions of CXCR-4, ICAM-1, and VEGF in 4 to 14 days after AMI. Immunohistochemistry analysis showed that rosuvastatin treatment was associated with increased accumulation of CD90+, CD133+, and c-kit+ progenitor cells in the peri-infarction region. Masson staining and echocardiograph confirmed that rosuvastatin could attenuate left ventricular remodeling and improve postinfarction systolic function.
  
  
  CONCLUSIONS
  The data suggest that rosuvastatin can protect the heart from ischemic injury and preserve the cardiac function in rats in vivo. The changing expressions of SDF-1, CXCR-4, ICAM-1, and VEGF, and the accumulation of progenitor cells were involved in this process.
authors.affiliation: Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Hu
authors.forename: Aijun
authors.initials: A
authors.lastname: Sun
authors.forename: Xinxing
authors.initials: X
authors.lastname: Xie
authors.forename: Zheyong
authors.initials: Z
authors.lastname: Huang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Jia
authors.forename: Ruiming
authors.initials: R
authors.lastname: Yao
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
mesh_terms: D000818:Animals; D016207:Cytokines / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D005464:Fluorobenzenes / Q000494:pharmacology / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology
chemical_list: D016207:Cytokines; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium