ABSTRACT
BACKGROUND: Regulatory T (Treg) cells play a protective role in atherosclerosis prone models and are related to the onset of acute coronary syndromes (ACS, including non-ST-elevation ACS (NSTEACS) and ST-elevation acute myocardial infarction (STEAMI)). CD4+LAP+ Treg cells are a novel subset of Tregs that have been found to ameliorate atherosclerosis in ApoE(-/-) mice, and these cells also exist in humans. The present study was designed to investigate whether CD4+LAP+ Treg cells are involved in the onset of ACS. METHODS: The frequencies of CD4+LAP+ and CD4+CD25+ Treg cells were detected using flow cytometric analysis, and the plasma IL-10 and TGF- ß 1 levels were measured using an ELISA in 29 stable angina (SA) patients, 30 NSTEACS patients, 27 STEAMI patients, and a control group (30 cases). RESULTS: The results revealed a significant decrease in the frequencies of CD4+LAP+ and CD4+CD25+ Treg cells and in the levels of IL-10 and TGF- ß 1 in patients with ACS compared with those in the SA and control groups. CONCLUSIONS: The decrease in the frequencies of CD4+LAP+ and CD4+CD25+ Treg cells may play a role in the onset of ACS.
Subject(s)
Acute Coronary Syndrome/immunology , Peptides/physiology , Protein Precursors/physiology , T-Lymphocytes, Regulatory/immunology , Transforming Growth Factor beta/physiology , Acute Coronary Syndrome/physiopathology , Aged , Down-Regulation , Female , Forkhead Transcription Factors/physiology , Humans , Interleukin-10/blood , Male , Middle Aged , Transforming Growth Factor beta1/blood , Ventricular Function, LeftABSTRACT
OBJECTIVE: To investigate the modulatory function of statin therapy on circulating microRNA-92a (miR-92a) in patients with coronary heart disease (CHD), and to evaluate the possibility of miR-92a as a new target of treatment for endothelial dysfunction. METHODS: A case control study was conducted. Prevalence of abnormal blood fat content, statin treatment rate, and attainment rate of low density lipoprotein-cholesterol (LDL-C) lowered to expected level in 236 patients with CHD were analyzed. Relationship between statin therapy in patients with type 2 diabetes mellitus (DM), and level of LDL-C and circulating miR-92a expression was analyzed by multivariate general linear factorial analysis. The incidence of acute coronary syndrome (ACS) was compared in patients with CHD receiving statin therapy in all groups. RESULTS: Prevalence of abnormal LDL-C was 95.7% (112/117) in CHD patients of non-statin therapy group, and 47.5% (112/236) of patients with CHD who should receive statin therapy but did not. Attainment rate of lowering of LDL-C to expected level in statin therapy group was 27.7% (33/119). LDL-C level (mmol/L) was significantly lower in statin therapy group than that in non-statin therapy group (2.457 ± 0.802 vs. 3.218 ± 1.130, Z = -9.760, P = 0.001), and incidence of ACS was significantly lower in statin therapy group than that in non-statin therapy group [33.6% vs. 71.8%, χ(2) = 34.491, P = 0.001]. There was no significant difference in incidence of ACS between patients with or without attaining the expected low value of LDL-C in statin therapy group [33.3% vs. 33.7%,χ(2) = 0.002, P = 0.968]. Circulating miR-92a expression was significantly higher in patients with stable angina pectoris (SAP) complicated with DM than those without DM (0.492 vs. -0.121, Z = -3.038, P = 0.002). It was found that statin therapy could down regulate miR-92a expression in patients with SAP complicated with DM as compared with that with non-statin therapy (0.419 vs. 0.687, Z = 1.289, P = 0.072). There was no significant difference in circulating miR-92a expression between statin therapy and non-statin therapy in patients with SAP without co-existing DM (-0.032 vs. -0.198, Z = -0.614, P = 0.539). Multivariate general linear factorial analysis showed that statin therapy was the major influential factor on LDL-C level in patients with CHD (F = 22.863, P = 0.001), and complicating DM was the major influential factor on circulating miR-92a expression in patients with SAP (F = 9.641, P = 0.003). CONCLUSION: Regulation of circulating miR-92a expression may be considered as a new clinical target for statin treating endothelial dysfunction in patients with CHD.
Subject(s)
Coronary Disease/blood , Coronary Disease/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , MicroRNAs/blood , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/complications , Aged , Case-Control Studies , Cholesterol, LDL/blood , Coronary Disease/complications , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Female , Humans , Male , Middle AgedABSTRACT
OBJECTIVE: To examine the expression of circulating microRNA-92a (miR-92a) in patients with ST-segment elevation myocardial infarction (STEMI), and the impact of percutaneous coronary intervention (PCI) on such expression. METHODS: The level of circulating miR-92a was measured in three groups of patients: 58 STEMI patients received PCI, 24 STEMI patients received no PCI, and 116 patients with stable angina pectoris (SAP) without PCI. RESULTS: On the day next to admission, STEMI patients received no PCI were found to have higher level of circulating miR-92a as compared to SAP patients without PCI (0.2869 ± 0.8167 vs. -0.0555 ± 0.9855, F = 2.438, P = 0.121). Twenty-four hours after the PCI, the level of circulating miR-92a in STEMI patients received the procedure was lower than those without it (-0.0324 ± 0.9563 vs. 0.2869 ± 0.8167, F = 2.054, P = 0.156). The SAP patients (without PCI) had higher survival rate as compared to the STEMI patients without PCI (100.0% vs. 75.0% P = 0.001), and the survival rate in STEMI patients received PCI was higher than those without it (89.7% vs. 75.0%, P = 0.088). CONCLUSIONS: In STEMI patients, the expression of circulating miR-92a is up-regulated. PCI therapy may suppress such up-regulation. Survival rate is higher in patients showing down-regulation of miR-92a. Our data suggest that miR-92a might have potential for diagnosis and therapeutic application in the prevention and treatment of STEMI.
