Upregulation of miR-155 in CD4(+) T Cells Promoted Th1 Bias in Patients With Unstable Angina.

An imbalance between T helper 1 (Th1) and T helper 2 (Th2) cells has been reported to increase plaque instability in patients with unstable angina (UA). MicroRNAs play a vital role in the differentiation of CD4(+) T cells. However, the role of microRNAs in regulation of Th1/Th2 balance in UA remains unclear. In this study, we aimed to elucidate microRNA expression profiles of circulating CD4(+) T cells in UA and to explore the function of microRNAs in the Th1/Th2 balance. A total of 53 patients with UA and 31 control subjects without coronary artery disease were enrolled. Microarray analysis of the microRNA expression profiles of CD4(+) T cells revealed that miR-155 was the most significantly upregulated microRNA of the 451 differentially expressed microRNAs. The upregulation of miR-155 expression was positively correlated with the percentage of Th1 cells and interferon-gamma (IFN-γ) levels in patients with UA. In addition, overexpression of miR-155 in human circulating CD4(+) T cells promoted Th1 differentiation. Further studies identified IFN-γ receptor alpha chain (IFN-γ Rα) mRNA as a direct and functional target of miR-155. A luciferase reporter assay verified that miR-155 directly targeted IFN-γ Rα mRNA. Small-interfering RNA-mediated knockdown of IFN-γ Rα mRNA showed effects similar to those of ectopic miR-155 expression. Thus, our study indicated that upregulation of miR-155 in circulating CD4(+) T cells in patients with UA promoted a shift in the Th1/Th2 balance toward Th1 dominance by repressing IFN-γ Rα, which may subsequently enhance plaque instability.

Effect of metoprolol on myocardial apoptosis and caspase-9 activation after coronary microembolization in rats.

OBJECTIVE: To explore the effect of metoprolol on myocardial apoptosis and caspase-9 activation after coronary microembolization (CME) in rats. METHODS: Forty rats were randomly divided into four groups (n=10 each): a sham operation (control) group, CME plus saline (CME) group, CME plus metoprolol (metoprolol) group and caspase-9 inhibitor Z-LEHD-FMK (ZLF) group. CME was induced by injecting 3000 polyethylene microspheres (42 µm diameter) into the left ventricle during a 10 s occlusion of the ascending aorta. Echocardiography, terminal deoxynucleotidyl transferase dUTP nick end labelling and Western blotting were used to evaluate cardiac function, apoptosis and activation of caspase-9/caspase-3, respectively, 6 h after CME. RESULTS: The echocardiographic parameters of left ventricular function were significantly decreased in the CME group compared with the control group (P<0.05); however, the metoprolol group and ZLF group showed significantly improved cardiac function compared with CME alone (P<0.05). Compared with the control group, the myocardial apoptosis rate and the levels of activated caspase-9 and -3 increased significantly in the CME group (P<0.05). Again, these effects were ameliorated by metoprolol and ZLF (P<0.05). CONCLUSIONS: The present study demonstrates that metoprolol and ZLF can protect the rat myocardium during CME by inhibiting apoptosis and improving cardiac function, likely by inhibiting apoptosis/ mitochondrial apoptotic pathway. These results suggest that antiapoptotic therapies may be useful in treating CME.

[Effects of pretreatment with metoprolol on cardiomyocyte apoptosis and caspase-8 activation after coronary microembolization in rats].

OBJECTIVE: To investigate the effects of metoprolol on cardiomyocyte apoptosis and caspase-8 activation after coronary microembolization(CME) in rats. METHODS: Adult rats were randomly assigned into CME group (intraventricular injection of 3000 microspheres with 42 µm in diameter), sham-operated group (0.1 ml saline) and CME plus metoprolol group (pretreatment with 3 bolus metoprolol 2.5 mg/kg intravenous injection at 10 minutes interval at 30 minutes before microspheres injection, n = 15, each group). Cardiac function was evaluated by echocardiography at 6 hours post various treatments. Cardiomyocyte apoptosis was detected with TUNEL staining and the expression of caspase-3 and caspase-8 was detected with Western blot analysis. RESULTS: Compared with sham-operated group, LVEF (72.68% ± 3.26% vs. 82.64% ± 3.43%, P < 0.05), fractional shortening (FS) (37.46% ± 2.38% vs. 42.85% ± 3.25%) and cardiac output (CO) [(0.101 ± 0.006) L/min vs. (0.162 ± 0.008) L/min] were significantly reduced while left ventricular end-diastolic diameter (LVEDd) [(6.22 ± 0.17) mm vs. (5.18 ± 0.43) mm] was significantly increased in CME group (all P < 0.05). Cardiac function [LVEF:73.94% ± 4.22%, FS:38.53% ± 2.03%, CO:(0.120 ± 0.012) L/min, LVEDd:(6.18 ± 0.27) mm] was similar in CME plus metoprolol group compared to CME group (all P > 0.05). The cardiomyocytes apoptosis rates (3.19% ± 1.23% vs. 0.18% ± 0.10%) and the levels of activated caspase-3 and caspase-8 proteins were significantly increased in CME group than in sham-operated group (all P < 0.05). The cardiomyocyte apoptosis rate (1.32% ± 0.28%) and the levels of activated caspase-3 and caspase-8 proteins were significantly lower in CME plus metoprolol group than in CME group (all P < 0.05). CONCLUSIONS: Metoprolol pretreatment reduced post-CME myocardial apoptosis possibly through downregulating death receptor-mediated apoptotic pathway.

Laser-structured microarray electrodes for durable stretchable lithium-ion battery.

Stretchable lithium-ion batteries (SLIBs) hold great potential as a power source for wearable electronics. A major challenge in the development of SLIBs is fabricating stable and reliable stretchable electrodes. Herein, we develop a novel laser-structured microarray electrodes based SLIBs. An active material film adhered to a planar stretchable current collector is ablated by ultrafast laser into an independent microscale square array, enabling electrodes stretchable. A one-dimensional elastic analytical model is developed to evaluate the stretchability of the microarray electrodes under tensile conditions. The microscale square array adheres to the current collector and keeps intact if the shear stress is less than the adhesion force as well as the tensile stress is less than the tensile strength of the active material. The demonstrated electrodes have a mass active material loading of 10 mg cm-2 and maintain robust electrochemical performance when stretched beyond 500 cycles at 100 % strains. The fabricated SLIBs show a stable capacity of 1.2 mAh cm-2, and over 70 % of initial capacity can be maintained at 100 % strain.

The Chinese version of the Health Professional Communication Skills Scale: Psychometric evaluation.

Objective: This study aims to translate the Health Professional Communication Skills Scale (HP-CSS) into Chinese and assess its psychometric properties. Methods: A total of 836 healthcare professionals were recruited. The demographic characteristics form and HP-CSS were used for data collection. The psychometric properties of HP-CSS were evaluated by examining item analysis, construct validity, known-group discriminant validity, internal consistency, and split-half reliability. Results: In terms of item analysis, the critical ratio (CR) of 18 items was both >3 (CR ranging from 9.937 to 28.816), and the score of each item was positively correlated with the total score (r ranging from 0.357 to 0.778, P < 0.001). The fit indices showed that the original correlated four-factor model of HP-CSS was adequate: χ2 =722.801; df = 126; χ2/df = 5.737; RMSEA = 0.075; CFI = 0.923; NNFI = 0.908; TLI = 0.906; IFI = 0.923. In terms of known-group discriminant validity, the HP-CSS total score was related to gender, occupation, work years, and communication skill training. Cronbach's α coefficient was 0.922, and the split-half reliability was 0.865 for the total scale. Conclusion: The Chinese version of the HP-CSS is a reliable and valid instrument to evaluate communication skills among healthcare professionals in China.

Altered expression of pro- and anti-inflammatory cytokines is associated with reduced cardiac function in rats following coronary microembolization.

Coronary microembolization (CME) is a spontaneous event in patients with ischemic heart disease and a potential iatrogenic complication in patients undergoing coronary interventions. CME induces an obvious inflammatory reaction, characterized by cellular infiltration, particularly of eosinophils, and multifocal microinfarcts. However, little is known on the correlation between pro- and anti-inflammatory cytokines and cardiac function following CME. In this study, microspheres with a diameter of 42 mum were intracoronarily injected into the apex of the left ventricle to induce CME (CME group). Rats injected with normal saline served as controls (sham operated control group). Expression of pro-inflammatory cytokines, TNF-alpha and IL-1beta, and an anti-inflammatory cytokine, IL-10, was measured at 3, 6, 12, 24 h, and 4 weeks post-injection by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. At the same time points, cardiac function and histological changes were evaluated by echocardiographic imagining and H&E staining, respectively. It was observed that the mRNA and protein expressions of TNF-alpha, IL-1beta, and IL-10 all started to increase at 3 h, reached to the peak levels at 12 h, and returned to the normal levels at 4 weeks post-injection. The left ventricular ejection fraction (LVEF) was significantly lower in the CME group than in the control group at 3, 6, 12, 24 h, and 4 weeks post-injection. Obvious myocardial microinfarcts with surrounding myocardial edema and degeneration, caryolysis, and infiltration of neutrophils and monocytes were observed in the CME group at 3, 6, 12, 24 h, and 4 weeks post-injection. Moreover, mRNA expression of TNF-alpha and IL-1beta was negatively correlated with LVEF, although not with myocardial microinfarcts, in the CME group. It is concluded that both protein and mRNA expression of TNF-alpha IL-1beta and IL-10 are dynamically changed following CME, which is associated with reduced cardiac function. Therefore, these cytokines may be potential therapeutic targets for clinical treatment of CME.

[Cardiomyocyte apoptosis and death receptor pathway in a rat model of coronary microembolization].

OBJECTIVE: To investigate the dynamic changes of cardiomyocyte apoptosis and the role of death receptor apoptotic pathway in a rat model of coronary microembolization (CME). METHODS: Adult rats were randomized to coronary microembolization (CME group, n = 63) or sham-operated group (S group, n = 55). CME model was established by aortic injection of 0.1 ml microspheres (42 microm, 3 x 10(4)/ml) into the left ventricle when the ascending aorta was temporarily clamped.S group received 0.1 ml saline injection and survived rats were randomly examined at 0, 3, 6, 12 and 24 hour post CME (n = 10 each). Heart function was evaluated by echocardiography. Myocardium sample was stained with hematoxylin-eosin and hematoxylin-basic fuchsin-picric acid to detect infarct areas. Cardiomyocyte apoptosis was detected with TUNEL staining. The expression of caspase-3 and caspase-8 was measured by Western blot analysis. RESULTS: Compared with S group, the left ventricular ejection fraction was significantly decreased and left ventricular end-diastolic diameter was significantly increased in CME group (all P < 0.05) except 0 hour CME group. The infarct sizes were similar in 3 hour, 6 hour, 12 hour, and 24 hour CME groups (P > 0.05). The apoptosis index (AI) in CME group were significantly higher at each time point compared to S group (P < 0.05) except 0 hour CME group and peaked at 6 hours. Apoptotic cardiomyocytes were found mainly in the myocardial microinfarcted area and border zones. The relative expression of caspase-3 and caspase-8 in CME group were both significantly increased at 3 hours and peaked at 6 hour post CME (P < 0.05). CONCLUSION: Cardiomyocytes apoptosis was significantly increased after coronary microembolization via activating death receptor apoptotic pathway in this coronary microembolization model.

Comparative efficacy and safety of drug-eluting stent and conventional therapies in coronary heart disease patients with in-stent restenosis: a meta-analysis.

We performed a meta-analysis to compare therapeutic outcome/safety of drug-eluting stent (DES) and conventional in-stent restenosis (ISR) treatments. We browsed through large volume of clinical data by searching MEDLINE, EMBASE, Cochrane central register of controlled trials, and EBSCO databases. In this study, 11 randomized controlled trials, 17 non-randomized controlled trials, 6,330 patients, and 6,662 lesions were included. Clinical and coronary angiography follow-up for 6-16 months was included. The major outcomes were target lesion revascularization (TLR) and major adverse cardiac events (MACE). We found that DES showed advantage in TLR (OR = 0.46; 95 % CI: 0.34, 0.62; P < 0.00001), MACE (OR = 0.51; 95 % CI: 0.34, 0.77; P = 0.001), Late Lumen Loss (IV = -0.30; 95 % CI: -0.44, -0.15; P < 0.0001), stenosis of lumen diameter (OR = -17.45; 95 % CI: -23.69, -11.21; P < 0.00001), and restenosis (OR = 0.26; 95 % CI: 0.17, 0.40; P < 0.00001) over conventional ISR treatment. Regarding cardiac death (OR = 0.80; 95 % CI: 0.55, 1.17; P = 0.25), myocardial infarction (OR = 1.00;95 %CI: 0.66, 1.51; P = 1.00) and late thrombosis (OR = 0.70; 95 % CI: 0.42, 1.17; P = 0.18), there was no significant difference between different treatments. We, therefore, concluded that in treating percutaneous coronary intervention-ISR, DES was more effective in reducing incidence of TLR, MACE, and restenosis, and decreasing severity of late lumen loss/stenosis of lumen diameter compared with bare metal stent, percutaneous transluminal coronary angioplasty, intracoronary brachytherapy, and cutting balloon treatments. There was no significant difference between DES and conventional therapy for ISR. As suggested by current statistical analysis, DES after ISR did not involve a higher incidence of cardiac death, myocardial infarction, and thrombosis.

Endothelial microparticles exert differential effects on functions of Th1 in patients with acute coronary syndrome.

BACKGROUND: Endothelial microparticles (EMPs) can be involved in inflammatory process, blood coagulation, and regulation of vascular function. However, it remains unclear whether EMPs participate in the pathogenesis of ACS. The purpose of this study is to investigate the impact of EMPs on Th1/Th2 development and functions in vitro. METHODS: Eight-five patients were allocated into SAP group (n=27), UAP group (n=28), and AMI group (n=30). Twenty hospitalized patients with normal coronary angiography were recruited as controls. The frequency of EMPs, IFN-γ, and IL-4 levels were measured, and the correlation between EMPs and Th1/Th2 cytokine was analyzed. PBMCs isolated from patients with ACS were treated in vitro with EMPs. This was followed by flow cytometry for Th1/Th2 counts, real-time PCR and western blotting for T-bet and GATA mRNA and protein expression, and ELISA for IFN-γ, TNF-α, IL-4, and IL-10. RESULTS: This study proved that the frequency of EMPs was significantly increased in ACS patients. There was a significant positive correlation between EMPs and IFN-γ. EMPs could significantly upregulate the differentiation and function of Th1 through increasing the expression of T-bet mRNA and protein. Furthermore, this study also indicated that EMP treatment in vitro could promote the expression of TNF-α, which exerts adverse effects on the pathogenesis and progression of atherosclerosis. CONCLUSIONS: EMPs may be involved in the immune and inflammatory processes that take part in artery atherosclerosis and that they do so by regulating Th1/Th2 differentiation and function. They may play an important role in the pathogenesis of coronary atherosclerosis and plaque instability.

Beta blocker metoprolol protects against contractile dysfunction in rats after coronary microembolization by regulating expression of myocardial inflammatory cytokines.

AIMS: To examine the effects of metoprolol on expression of myocardial inflammatory cytokines and myocardial function in rats following coronary microembolization (CME). MAIN METHODS: Male rats were randomly assigned to receive either sham-operation (control group), CME plus saline (CME group), or CME plus metoprolol (metoprolol group). CME was induced by injecting 3000 polyethylene microspheres (42 µm) into the left ventricle during a 10-second occlusion of the ascending aorta. Metoprolol (2.5mg/kg) or saline was administered as three intravenous bolus injections after CME. At 3h, 6h, 12h, 24h and 4 weeks after CME, myocardial function was measured with echocardiography; and the mRNA and protein levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and interleukin 1-ß (IL-1ß) were determined. KEY FINDINGS: Induced CME led to markedly higher mRNA and protein levels of TNF-α, IL-1ß and IL-10 at 3, 6, 12, and 24h, as well as reduced left ventricular function, compared to the control group. Metoprolol administration reduced TNF-α and IL-1ß levels, but increased IL-10 levels at 3, 6, 12, and 24h compared to the CME group. Moreover, metoprolol treatment resulted in significantly improved left ventricular function at 12h, 24h and 4 weeks, but afforded no cardiac protection at 3h and 12h, compared to the CME group. SIGNIFICANCE: Higher levels of TNF-α and IL-1ß in rats following CME are associated with the development of myocardial contractile dysfunction. Metoprolol-conferred protection against progressive contractile dysfunction following CME may be mediated by its anti-inflammation potential.

Drug-eluting stents vs. intracoronary brachytherapy for in-stent restenosis: a meta-analysis.

BACKGROUND: It has been reported that drug-eluting stents (DES) were superior to intracoronary brachytherapy (ICBT) in patients with in-stent restenosis (ISR). However, it is unknown whether there might be differences between DES and ICBT in terms of efficacy and safety in large sample size and long-term follow-up. HYPOTHESIS: The aim of this study was to determine whether DES implantation remains favorable in large sample size and long-term follow-up when compared with ICBT among patients with ISR. METHODS: We conducted a search in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials without language restrictions. A meta-analysis of 1942 cases from 12 controlled trials of DES vs ICBT for ISR was performed. RESULTS: Drug-eluting stents were significantly more effective in reducing target-vessel revascularization (TVR) (odds ratio [OR]: 0.44, 95% confidence interval [CI]: 0.23-0.81, P = 0.009) and binary restenosis (OR: 0.34, 95% CI: 0.26-0.46, P<0.00001) compared with ICBT at midterm follow-up. There were no significant differences between DES and ICBT in cardiac death, myocardial infarction (MI), and late stent thrombosis at midterm follow-up. A statistical significance has been found between the 2 groups in TVR (OR: 0.61, 95% CI: 0.43-0.86, P = 0.005) at long-term follow-up. There were no significant differences in cardiac death and MI between the 2 groups at long-term follow-up. CONCLUSIONS: These findings provide evidence that DES is superior to ICBT for the treatment of ISR in TVR and binary restenosis reduction, but not in cardiac death, MI, and late stent thrombosis reduction. © 2011 Wiley Periodicals, Inc. Yong-Guang Lu, MD, and Yan-Mei Chen, MD, contributed equally to this work. The authors have no funding, financial relationships, or conflicts of interest to disclose.

Effect of atorvastatin (Lipitor) on myocardial apoptosis and caspase-8 activation following coronary microembolization.

We determined the effect of atorvastatin on myocardial apoptosis and caspase-8 activation following coronary microembolization (CME) in a rat model. For this, 50 rats were randomly and equally divided into CME; sham-operated (control); atorvastatin lavage; gastric lavage control; and caspase-8 inhibitor (CHO) groups. In CME animals, a microembolization ball was injected through the left ventricle. Sham animals were injected with normal saline (NS). Atorvastatin group received atorvastatin gastric lavage once-a-day, 1 week before surgery. Gastric lavage controls had similar lavage with NS. CHO group was i.p-injected (CHO: 10 mg/kg) 30 min before surgery. Cardiac indices in each group were determined by echocardiography 6-h postoperatively. TUNEL assay and western blot were used for myocardial apoptosis and expression of caspases-3/-8, respectively. Echocardiography data show that left ventricular ejection fraction (LVEF) in CME group was significantly decreased (P < 0.05) compared with sham controls. Besides, left ventricular fractional shortening (FS) and cardiac output (CO) were also decreased with an increase in left ventricular end-diastolic dimension (LVEDd). Atorvastatin and CHO animals had significantly improved (P < 0.05) cardiac function compared with CME group. Myocardial apoptosis and activation levels of caspases-3/-8 were significantly increased (P < 0.05) compared with sham; myocardial apoptosis and activation levels of caspases-3/-8 were significantly decreased (P < 0.05) in atorvastatin and CHO groups compared with CME group. In conclusion, atorvastatin pretreatment suppressed post-CME myocardial apoptosis and improved cardiac function through the blockade of a myocardial death receptor-mediated apoptotic pathway.