Shao-Jie Bi1, Chun-Yan Wang2, Juan Zhang1, Zhao-Peng Lv1, Yi-Xin Li3. 1. Department of Cardiology, Second Hospital of Shandong University Ji'nan 250033, Shandong Province, China. 2. Department of Emergency Medicine, Second Hospital of Shandong University Ji'nan 250033, Shandong Province, China. 3. Department of Radiology, Second Hospital of Shandong University Ji'nan 250033, Shandong Province, China.
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.
RCT Entities:
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.