title: Atorvastatin up-regulates TRIB3 independent of ATF4-CHOP pathway in atherosclerotic patients.
abstract: BACKGROUND
  Macrophage apoptosis triggered by endoplasmic reticulum (ER) stress contributes much to atherosclerosis, especially plaque vulnerability. Activating transcription factor 4 (ATF4)-CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP)-Tribbles 3 (TRIB3) pathway is closely related to the ER stress. This study aimed to investigate the effect of atorvastatin on the ATF4-CHOP-TRIB3 pathway.
  
  
  METHODS
  Forty-seven patients were randomized into 80-mg and 20-mg atorvastatin group. Follow-up was performed at weeks 6 and 12, and complete blood chemistry, lipid assay and detection of 5 target genes (tumor protein 53, ATF4, C/EBP, CHOP and TRIB3) in monocytes/macrophages were conducted. Furthermore, the interaction between dosage and duration of therapy was evaluated.
  
  
  RESULTS
  After 12-week therapy, patients in both groups experienced significant reductions in ATF4 (P=0.038) and C/EBP (P=0.003) expressions. Tumor protein 53 (P=0.015) and TRIB3 (P=0.045) expressions increased markedly in 80-mg atorvastatin group. However, there was no significant difference in CHOP expression at three time-points and between atorvastatin groups. Moreover, there was no interaction between dosage and duration of therapy.
  
  
  CONCLUSIONS
  Atorvastatin has an effect on ER stress through ATF4-CHOP pathway. Atorvastatin at a high dose is more likely to increase TRIB3 expression, but this warrants further investigation.
authors.affiliation: Department of Cardiology, Second Hospital of Shandong University Ji'nan 250033, Shandong Province, China.
authors.forename: Shao-Jie
authors.initials: SJ
authors.lastname: Bi
authors.affiliation: Department of Emergency Medicine, Second Hospital of Shandong University Ji'nan 250033, Shandong Province, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Second Hospital of Shandong University Ji'nan 250033, Shandong Province, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Second Hospital of Shandong University Ji'nan 250033, Shandong Province, China.
authors.forename: Zhao-Peng
authors.initials: ZP
authors.lastname: Lv
authors.affiliation: Department of Radiology, Second Hospital of Shandong University Ji'nan 250033, Shandong Province, China.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Li
keywords: Atherosclerosis; atorvastatin; monocyte; tribbles 3