Abstract 11510: Atorvastatin Affects Expression of Sirt1 via Microrna-34a in Circulating Their Progenitor Cells Get Pirated From be with Coronary Artery Disease
Background: Endothelial senescence is thought to play a role in coronary artery disease (CAD). MicroRNA-34a (miR-34a) has recently been found to target class III deacetylase, silent information regulator 1 (SIRT1), leading to endothelial senescence. We investigated whether miR-34a and SIRT1 were expressed in endothelial progenitor cells (EPCs) obtained from patients with CAD, and whether statin (atorvastatin or rosuvastatin) might affect these levels.
Methods: To determine the effects of miR-34a on SIRT1, human endothelial cells transfected with miR-34a mimic and inhibitors were analyzed for phospho-SIRT1 levels. EPCs were obtained from 70 patients with CAD (mean age, 67.9 ± 9.1; male / female, 56 / 14) and 48 subjects without CAD (mean age, 65.1 ± 8.7; male / female, 37 / 11) as control. Patients with CAD were randomized to 12 months of a treatment with atorvastatin (n = 35, 10 mg / day) or rosuvastatin (n = 35, 2.5 mg / day). EPCs were obtained from peripheral blood at baseline and after 12 months of statin therapy. Levels ofmiR-34a and SIRT1 in EPCs were measured by real-time RT-PCR and fluorescence-activated cell sorting.
Results: Function approaches to miR-34a have shown that transfection of miR-34a into endothelial cells resulted in regulation of phospho-SIRT1 expression. Levels of miR-34a were higher in CAD group than in control (2.86 ± 1.57 vs. 1.43 ± 0.83, P < 0.05). Levels of phospho-SIRT1 were lower in CAD group than in controls (14.1 ± 2.3 vs. 18.2 ± 3.4, P < 0.05). Levels of miR-34a were mildly negatively correlated with phospho-SIR1 levels in all subjects (r = -0.47, P < 0.01). A randomized clinical study has shown that atorvastatin group markedly decreased miR-34a and increased phospho-SIRT1 levels (miR-34a; 2.91 ± 1.42 vs. 1.70 ± 1.29: phospho-SIRT1; 14.2 ±2.5 vs. 13.8 ± 1.9: Baseline vs. 12 months, all P < 0.05), whereas rosuvastatin group did not change these levels (miR-34a; 2.81 ± 1.73 vs. 2.87 ± 1.44: phospho-SIRT1; 13.9 ± 2.1 vs. 15.9 ± 2.8: Baseline vs. 12 months, not significant).
Conclusions: This study suggests that atorvastatin upregulates SIRT1 expression via inhibiting miR-34a in CAD patients, possibly contributing to the beneficial effects of atorvastatin on endothelial function in this disorder.
- © 2011 by American Heart Association, Inc.