MicroRNA 199a Is Downregulated in Patients After Coronary Artery Bypass Graft Surgery and Is Associated with Increased Levels of Sirtuin 1 (SIRT 1) Protein and Major Adverse Cardiovascular Events at 3-Year Follow-Up

冠状动脉搭桥手术后患者中 microRNA 199a 下调,并与 3 年随访中 Sirtuin 1 (SIRT 1) 蛋白水平升高和主要不良心血管事件相关

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作者:Aylin Hatice Yamac, Mustafa Ahmet Huyut, Emre Yilmaz, Ilke Celikkale, Ahmet Bacaksiz, Yusuf Demir, Ali Riza Demir, Mehmet Erturk, Nijad Bakhshaliyev, Ramazan Ozdemir, Ulkan Kilic

Abstract

BACKGROUND The cardioprotective protein SIRT1 is elevated in patients with coronary artery disease (CAD) to compensate for the disease-related adverse effects, but less is known about the prognostic role of SIRT 1 regulating microRNAs in patients after coronary artery bypass graft (CABG) surgery. MATERIAL AND METHODS The expression of the SIRT 1-specific microRNAs miR-199a and miR-195 was analyzed using real-time PCR in 68 patients referred for CABG surgery and 34 control patients undergoing heart valve surgery. In CABG patients, major adverse cardiac and cerebrovascular events (MACCEs), including all-cause death, myocardial infarction (MI), re-vascularization, heart failure symptoms ≥NYHA II, re-hospitalization for any cardiovascular reason, and stroke, were analyzed at a median follow-up (FU) of 3.2 years (range: 3.0-3.6). RESULTS The level of miR-199a in patients with CAD was significantly reduced compared to the control group (relative expression: 0.89±0.49 vs. 1.90±0.90, p=0.001), while SIRT 1 protein was markedly enhanced (p<0.001). In patients undergoing CABG who had MACCEs, miR-199a was significantly lower compared to patients with an uneventful FU (0.71±0.25 vs. 0.98±0.53, p=0.007). Heart failure status, death, and total MACCEs rate were inversely correlated with the amount of miR-199a (p=0.039) at 3-year FU. CONCLUSIONS Altered expression of miR-199a in myocardial tissue was found to be associated with SIRT 1 upregulation in patients with CAD undergoing CABG and was associated with an increased MACCEs rate at mid-term follow-up.

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