Expression of miR-23a induces telomere shortening and is associated with poor clinical outcomes in patients with coronary artery disease
| Autor: | Motoyuki Nakamura, Mamoru Satoh, Sho Hitomi, Yoshihiro Morino, Takuya Osaki, Takahito Nasu, Yuji Takahashi |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty General Medicine Transfection Biology medicine.disease Peripheral blood mononuclear cell Surgery Telomere Coronary artery disease 03 medical and health sciences 030104 developmental biology Internal medicine microRNA medicine Pitavastatin Coronary atherosclerosis Telomeric-Repeat Binding Factor medicine.drug |
| Zdroj: | Clinical Science. 131:2007-2017 |
| ISSN: | 1470-8736 0143-5221 |
| DOI: | 10.1042/cs20170242 |
| Popis: | Telomeric repeat binding factor (TRF) 2 (TRF2) plays an important role in telomere maintenance. miR-23a may directly inhibit TRF2 expression, thereby, inducing telomere shortening and cellular senescence. The present study aimed to determine whether miR-23a and TRF2 are expressed in patients with coronary artery disease (CAD), and whether pitavastatin might affect these levels. The present study included 104 patients with CAD and 50 controls. Patients with CAD were randomly divided into two subgroups (a moderate lipid lowering therapy (LLT) group and an aggressive LLT group). Peripheral blood mononuclear cells (PBMCs) were taken from patients with CAD and from controls at baseline and after 12 months. Levels of miR-23a were higher in the CAD group than in the controls. Levels of TRF2 protein were lower in the CAD group than in the controls. Our randomized clinical study showed that aggressive LLT decreased miR-23a and increased TRF2 levels, whereas moderate LLT generated no change in these levels. Our transfected cell model showed that miR-23a controlled TRF2 expression. After a mean follow-up of 339 days, cardiovascular events were associated with high miR-23a , low TRF2 or low relative telomere length. Multivariate analysis showed that levels of miR-23a (RR: 4.9, 95% CI: 1.9–14.3) were a strong predictor of cardiovascular events after adjustment for baseline characteristics. In conclusion, elevated levels of miR-23a play an important role in coronary atherosclerosis via down-regulated TRF2, and may provide important prognostic information in patients with CAD. Additionally, aggressive LLT may prevent telomere erosion via down-regulated miR-23a . |
| Databáze: | OpenAIRE |
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