Expression of Induces Telomere Shortening and is Associated with Poor Clinical Outcomes in Patients with Coronary Artery Disease

Telomeric repeat binding factor (TRF) 2 (TRF2) plays an important role in telomere maintenance. may directly inhibit TRF2 expression, thereby, inducing telomere shortening and cellular senescence. The present study aimed to determine whether 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 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 and increased TRF2 levels, whereas moderate LLT generated no change in these levels. Our transfected cell model showed that controlled TRF2 expression. After a mean follow-up of 339 days, cardiovascular events were associated with high , low TRF2 or low relative telomere length. Multivariate analysis showed that levels of (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 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 .