title: Rosuvastatin attenuates atrial structural remodelling in rats with myocardial infarction through the inhibition of the p38 MAPK signalling pathway.
abstract: OBJECTIVE
  The purpose of this study was to verify the hypothesis that rosuvastatin attenuates atrial structural remodelling in rats with myocardial infarction (MI) through the regulation of the p38 mitogen-activated protein kinase (MAPK) signalling pathway.
  
  
  METHODS
  A total of 66 rats were used in this study to establish a model of MI. The 56 rats that survived the first 24h after surgery were randomly divided into four groups: the control group (C group), the rosuvastatin group (R group), the low-dose torasemide group (T1 group), and the high-dose torasemide group (T2 group). The four groups of rats received daily intragastric administration of normal saline, rosuvastatin, or torasemide (T1: 1mg/kg body weight; T2: 2mg/kg body weight) for a total of four weeks. The rats in the sham-operated group (n=14) also received daily intragastric administration of normal saline for four weeks. After four weeks of intervention, the left ventricular end-diastolic pressure (LVEDP) was measured in all groups of rats by haemodynamic methods. The rats were then sacrificed, and the left atrial tissues were collected. The collagen volume fractions (CVFs) in the left atrial tissues were determined using Masson's trichrome staining. The expression of phosphorylated p38 (P-p38) MAPK in the left atrial tissues was examined by immunohistochemistry and western blot analysis.
  
  
  RESULTS
  The results showed that LVEDP, CVF, and P-p38 MAPK expression were drastically elevated in the four MI groups in comparison to the sham-operated group (p<0.001). Rosuvastatin elevated the left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF). Both rosuvastatin and torasemide improved the haemodynamic parameters. No significant difference was detected in LVEDP between the R group and the T1 group (p=0.37). In contrast, LVEDP was significantly higher in the R group than in the T2 group (p <0.05). CVF (%) was markedly decreased in the R group compared to the C, T1, and T2 groups (decreased by 47.4%, 28%, and 20.1%, respectively). Immunohistochemical analysis showed that the indices of P-p38 MAPK positive cells were significantly decreased in the R group in comparison with the C, T1, and T2 groups (decreased by 44.6%, 36.6%, and 21.4%, respectively). Western blot analysis demonstrated that P-p38 MAPK expression was markedly reduced in the R group compared with the C and T1 groups (reduced by 67% and 40.5%, respectively). The level of P-p38 MAPK in the R group was slightly higher than in the T2 group. However, the difference was not statistically significant (p>0.05).
  
  
  CONCLUSIONS
  Rosuvastatin attenuates atrial structural remodelling in rats with MI. The mechanism underlying this phenomenon may be associated with the downregulation of P-p38 MAPK by rosuvastatin.
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China; Department of Cardiology, People's Hospital of Liaocheng, Liaocheng 252000, PR China.
authors.forename: Mengzan
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Shandong Provincial Taishan Hospital, Taian 271000, PR China; Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Echocardiography, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors.forename: Xinxing
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors.forename: Ximin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China. Electronic address: houyinglongjinan@hotmail.com.
authors.forename: Yinglong
authors.initials: Y
authors.lastname: Hou
mesh_terms: D000818:Animals; D064752:Atrial Remodeling / Q000187:drug effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D000068718:Rosuvastatin Calcium / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000068718:Rosuvastatin Calcium; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Atrial structural remodeling; Myocardial infarction; Rosuvastatin; p38 MAPK