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

Abstract

BackgroundThe 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/MethodsThe 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).ResultsThe 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.ConclusionsAltered 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.

Protective effect of microRNA‑381 against inflammatory damage of endothelial cells during coronary heart disease by targeting CXCR4

“…resting endothelial cells express no or low levels of adhesion molecules and are resistant to leukocyte recruitment. However, various cHd stimulants, including TnF-α, il-1β or oX-ldl, activate the endothelial inflammatory cascade (41). The present study revealed that overexpression of miR-381 significantly promoted oX-ldl-induced HuVec proliferation, decreased apoptosis and suppressed the inflammation response, whereas downregulation of mir-381 exhibited the opposite effect.…”

“…a previous study demonstrated that mirnas serve important roles in many biological activities, including cell proliferation, inflammation and apoptosis (38). in cHd, mir-423, mir-23 and mir-199a have been reported to serve as biomarkers for therapeutic targets (39)(40)(41). mir-381 has been reported to be dysregulated in various cancers (20)(21)(22), but few studies have focused on the role of mir-381 in cHd.…”

Oxidative Stress-Responsive MicroRNAs in Heart Injury

“…Inhibition of miRNA-92a attenuates oxidative stress and improves endothelial function through enhancing HO-1 expression and activity in diabetic mouse aortas [138]. Yamac et al observed markedly lowered expression of miRNA-199a in patients with coronary artery disease [139]. In parallel, they also showed the induction of cardioprotective protein SIRT1, a potential target of miRNA-199.…”

“…Endothelial cell apoptosis under oxidative stress plays a critical role in the initiation and progression of atherosclerosis [131][132][133][134][135][136][137][138][139][140][141]. Li et al observed that overexpression of miRNA-210 caused inhibition of apoptosis and reduction of ROS level in human umbilical vein endothelial cells (HUVECs) treated with H 2 O 2 and also downregulation of caspase levels.…”

“…A brief review of selected miRNAs included in the cardiovascular diseases caused by oxidative stress is provided in Table 1. miRNA-199a Downregulated SIRT1 [139] Heart failure miRNA-199b Upregulated calcineurin/NFAT [101,[157][158][159] miRNA-21 Upregulated natriuretic peptide B [156,163] Mef2a-Myocyte-specific enhancer factor 2A, Gata4-Transcription factor GATA-4, GDP-GTP exchange protein-guanosine diphosphate-guanosine triphosphate exchange protein, Cdc42-Cell division control protein 42, Myh7-beta myosin heavy chain, Keap1/Nrf2-Kelch-like ECH-associated protein 1/Nuclear factor erythroid 2-related factor 2, FoxO1-Forkhead box protein O1, Mcl-1-Myeloid cell leukemia 1, MnSOD-manganese-dependent superoxide dismutase, NF-κB-nuclear factor kappa B, TNF-α-tumor necrosis factor alpha, S1P1-Sphingosine-1-phosphate receptor 1, MKK4-Mitogen-activated protein kinase kinase 4, eNOS-Endothelial nitric oxide synthase, INF receptor-interferon receptor, Ogt-O-linked β-N-acetylglucosamine transferase, HO-1-Heme oxygenase 1, SIRT1-sirtuin 1, NFAT-Nuclear factor of activated T cells.…”