title: Cilostazol Prevents Atrial Structural Remodeling through the MEK/ERK Pathway in a Canine Model of Atrial Tachycardia.
abstract: OBJECTIVE
  Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. Atrial structural remodeling (ASR), particularly atrial fibrosis, is an important contributor to the AF substrate. This study aimed to investigate the preventive effects of the phosphodiesterase 3 inhibitor cilostazol on ASR and its potential molecular mechanisms in a canine model of rapid atrial pacing (RAP).
  
  
  METHODS
  Thirty dogs were assigned to sham (Sham), paced/ no treatment (Paced) and paced + cilostazol 5 mg/kg/day (Paced + cilo) groups, with 10 dogs in each group. RAP at 500 beats/min was maintained for 2 weeks, while the Sham group was instrumented without pacing. Cilostazol was provided orally during pacing. Western blotting, RT-PCR and pathology were used to assess ASR.
  
  
  RESULTS
  Cilostazol attenuated atrial interstitial fibrosis and structural remodeling in canines with RAP. MEK/ERK transduction pathway gene expression was upregulated in the Paced group compared with the Sham group. Cilostazol markedly alleviated these changes in the MEK/ERK pathway. Transforming growth factor-β1 protein expression in the Paced group was significantly higher than in the Sham group (p < 0.01), and was significantly reduced by cilostazol (p < 0.01).
  
  
  CONCLUSIONS
  Our findings suggest that cilostazol is beneficial for prevention and treatment in atrial tachycardia-induced ASR in a canine model of RAP.
authors.affiliation: Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Xinghua
authors.initials: X
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Meng
authors.initials: M
authors.lastname: Yuan
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.forename: Guangping
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D064752:Atrial Remodeling / Q000187:drug effects*; D000077407:Cilostazol; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006325:Heart Atria / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D058987:Phosphodiesterase 3 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D013617:Tachycardia, Supraventricular / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D058987:Phosphodiesterase 3 Inhibitors; D013777:Tetrazoles; D053773:Transforming Growth Factor beta1; D000077407:Cilostazol