EEF1A2 accelerates the protein translation of chemokine in rat myocardial cells induced by ischemia-reperfusion.

How to reduce the damage caused by myocardial ischemia-reperfusion (IR) in a timely manner to save patients' lives is still a great clinical challenge. Although dexmedetomidine (DEX) has been reported to protect the myocardium, the regulatory mechanism of gene translation responding to IR injury and DEX protection is poorly understood. In this study, IR rat model with DEX and the antagonist yohimbine (YOH) pretreatment were established, and RNA sequencing was carried out to seek the important regulators in differential expressed genes. A series of cytokines and chemokine as well as eukaryotic translation elongation factor 1 alpha 2 (EEF1A2) were induced by IR compared to control and compromised by DEX pretreatment compared to IR, then reversed by YOH. Immunoprecipitation was conducted to identify that peroxiredoxin 1 (PRDX1) interacted with EEF1A2 and contributed to the recruitment of EEF1A2 on mRNA molecules of cytokines and chemokine. Knockdown of PRDX1 could weaken the enhancive effect of EEF1A2 for gene translation of IL6, CXCL2 and CXCL11 under the IR condition, and indeed reduce cell apoptosis of cardiomyocytes. We also determined that the RNA motif "USCAGDCU" at 5' UTR could be particularly recognized by PRDX1. Destruction of this motif at the 5' UTR of IL6, CXCL2 and CXCL11 by CRISPR-CAS9 could result in the loss occupancies of EEF1A2 and PRDX1 on the mRNA of these three genes. Our observations showed the importance of PRDX1 in the reasonable control of cytokine and chemokine expression to prevent excessive inflammatory response to cell damage.

Inhibition of MicroRNA-23 Contributes to the Isoflurane-Mediated Cardioprotection Against Oxidative Stress.

Isoflurane is one of the most frequently used volatile anesthetics in clinical practice for inhalational anesthesia. It is widely studied that isoflurane mediates cardioprotection during multiple pathological processes. However, the precise mechanisms have not been fully elucidated. Neonatal cardiomyocytes were isolated and cultured, followed by treatments with isoflurane at 0, 50, 100 or 200 µM. Rat cardiomyoblast cell line, H9c2, was treated with H2O2. Expression of miR-23 was measured by qRT-PCR. The cell survival rate of H9c2 in response to H2O2 treatments was evaluated by MTT assay. The ROS and GSH/GSSG levels were measured using Superoxide Detection Kit and GSH/GSSG Ratio Detection Assay Kit. In this study, we report an isoflurane-miR-23-antioxidant axis in cardiomyocyte. We observed that miR-23 was suppressed by isoflurane treatments at 50, 100 or 200 µM. Moreover, cardiomyocyte with isoflurane exposure was insensitive to H2O2 treatment in vitro. Inhibition of miR-23 protected cardiomyocyte against oxidative stress induced by H2O2 treatments at 30, 60, 90 or 120 µM. In addition, overexpression of miR-23 induced ROS generation over twofolds and rendered cardiomyocyte sensitive to H2O2 treatments. We demonstrate that miR-23 inhibited intracellular GSH, an antioxidant against oxidative stress. Our results reveal that with isoflurane exposure, overexpression of miR-23 rendered cardiomyocyte sensitive to H2O2 treatments at 20, 30, 40, 50 µM. Pretreatments with GSH in miR-23 overexpressing cells rescued the cell death under oxidative stress. In summary, our results illustrate that the isoflurane-mediated protection of cardiomyocytes under oxidative stress is through inhibition of miR-23. This study provides an aspect for the miRNAs-modulated cardiomyocyte sensitivity to oxidative stress, contributing to the development of therapeutic agents.

Chronotropic Incompetence and its Relation to Exercise Intolerance in Chronic Obstructive Pulmonary Disease.

BACKGROUND: To study the relationship between chronotropic incompetence (CI) and disease severity and to assess the effect of CI on exercise capacity in patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Arterial blood gas analysis, pulmonary function test and cardiopulmonary exercise testing were conducted in 60 patients with stable COPD and 45 healthy volunteers. CI was defined using the chronotropic response index (CRI = (peak heart rate-resting heart rate) / (220-age-resting heart rate). Based on CRI, patients with COPD were divided into the normal chronotropic group (n = 23) and CI group (n = 37). RESULTS: CI was present in 61.7% of the patients with COPD. Exercise capacity (peak oxygen uptake as percentage of predicted value, peak VO2%pred), peak heart rate and CRI were significantly lower in patients with COPD than in controls. However, resting heart rate was significantly higher than in controls. FEV1%pred and exercise capacity were significantly decreased in the CI group when compared with those in the normotropic group. There was significant association between CRI with FEV1%pred and peak VO2%pred. Multivariate regression analysis showed that CRI and FEV1%pred were independent predictors of exercise capacity in patients with COPD. A cutoff of 0.74 for the CRI showed a specificity of 94.1% in predicting patients with a peak VO2%pred < 60%. CONCLUSIONS: CRI was associated with disease severity in patients with COPD. CI may be an important parameter to reflect exercise capacity in patients with COPD.

[Association of oxygen uptake efficiency in exercise test with exercise capacity in patients with stable chronic obstructive pulmonary disease].

OBJECTIVE: To explore the characteristics of oxygen uptake efficiency (OUE) in patients with chronic obstructive pulmonary disease (COPD), and to analyze the relationship between OUE and the exercise capacity. METHODS: Pulmonary function test and cardiopulmonary exercise test were performed in 59 patients with stable COPD (grade I, n = 15; grade II, n = 16; grade III, n = 19; grade IV, n = 9) and 29 healthy volunteers of the same age. Their successive breathing respiratory exchange parameters were collected and analyzed. t test and χ(2) test were used for 2 sample comparison, while multiple comparisons among groups were performed by using single factor analysis of variance. Correlation analysis was done by Pearson correlation test. RESULTS: Compared with the normal control group [(2.2 ± 0.4) L·min(-1)·lg(L·min(-1))(-1); (35 ± 4) ml/L], the OUES and OUEP of the COPD patient group [(1.9 ± 0.3) L·min(-1)·lg(L·min(-1))(-1); (31 ± 5) ml/L]were significantly lower (t = 4.57, 3.39, all P < 0.01) . The OUE of the grade I patients showed no significant difference compared with the normal control group (t = 0.36-1.49, all P > 0.05), while the OUES of the grade II-IV patients [(2.05 ± 0.26), (1.76 ± 0.28) and (1.63 ± 0.19) L·min(-1)·lg(L·min(-1))(-1)] decreased significantly compared to the normal control group [(2.23 ± 0.39) L·min(-1)·lg(L·min(-1))(-1); t = 2.42-5.26, all P < 0.05]. The OUEP and the OUE at the anaerobic threshold of the grade II-III patients [(31 ± 4) and (31 ± 5), (29 ± 5) and (29 ± 5) ml/L] decreased significantly compared to the normal control group [(35 ± 4) and (34 ± 4) ml/L, t = 2.18-4.83, all P < 0.05]. The OUES, OUEP and the OUE at the anaerobic threshold in COPD patients were correlated (r = 0.500-0.625, all P < 0.01) positively with the exercise tolerance (peak VO2% pred). CONCLUSIONS: The oxygen uptake efficiency of patients with COPD is significantly reduced compared to that of the normal subjects, and is correlated positively with the exercise capacity.