Silencing of ATP2B1-AS1 contributes to protection against myocardial infarction in mouse via blocking NFKBIA-mediated NF-κB signalling pathway.

Myocardial infarction (MI) is an acute coronary syndrome that refers to tissue infarction of the myocardium. This study aimed to investigate the effect of long intergenic non-protein-coding RNA (lincRNA) ATPase plasma membrane Ca2+ transporting 1 antisense RNA 1 (ATP2B1-AS1) against MI by targeting nuclear factor-kappa-B inhibitor alpha (NFKBIA) and mediating the nuclear factor-kappa-B (NF-κB) signalling pathway. An MI mouse model was established and idenepsied by cardiac function evaluation. It was determined that ATP2B1-AS1 was highly expressed, while NFKBIA was poorly expressed and NF-κB signalling pathway was activated in MI mice. Cardiomyocytes were extracted from mice and introduced with a series of mouse ATP2B1-AS1 vector, NFKBIA vector, siRNA-mouse ATP2B1-AS1 and siRNA-NFKBIA. The expression of NF-κBp50, NF-κBp65 and IKKß was determined to idenepsy whether ATP2B1-AS1 and NFKBIA affect the NF-κB signalling pathway, the results of which suggested that ATP2B1-AS1 down-regulated the expression of NFKBIA and activated the NF-κB signalling pathway in MI mice. Based on the data from assessment of cell viability, cell cycle, apoptosis and levels of inflammatory cytokines, either silencing of mouse ATP2B1-AS1 or overexpression of NFKBIA was suggested to result in reduced cardiomyocyte apoptosis and expression of inflammatory cytokines, as well as enhanced cardiomyocyte viability. Our study provided evidence that mouse ATP2B1-AS1 silencing may have the potency to protect against MI in mice through inhibiting cardiomyocyte apoptosis and inflammation, highlighting a great promise as a novel therapeutic target for MI.

MiR-128-3p accelerates cardiovascular calcification and insulin resistance through ISL1-dependent Wnt pathway in type 2 diabetes mellitus rats.

Vascular calcification is highly prevalent in patients with type 2 diabetes mellitus (T2DM), one of the most common chronic diseases with high morbidity and mortality. In recent years, microRNAs have been widely reported as potential biomarkers for the diagnosis and treatment of T2DM. We hypothesized that miR-128-3p is associated with cardiovascular calcification and insulin resistance (IR) in rats with T2DM by targeting ISL1 via the Wnt pathway. Microarray analysis was adopted to identify differentially expressed genes related to T2DM. T2DM models were induced in rats. Blood samples from normal and T2DM rats were used to detect islet ß-cell function, islet sensitivity, and calcium content. Next, islet tissues were obtained to identify the expression of miR-128-3p, ISL1, and the Wnt signaling pathway- and apoptosis-related genes. Finally, apoptosis of islet ß-cells was determined by flow cytometry. Through microarray analysis of GSE27382 and GSE23343, ISL1 was found to be downregulated in T2DM. In blood samples from T2DM rats, basic biochemical indicators, IR, and calcium content were increased, and islet sensitivity and islet ß-cell function were decreased. Furthermore, upregulation of miR-128-3p and ISL1 gene silencing promoted the expression of Wnt-1, ß-catenin, GSK-3ß, and Bax and the phosphorylation of ß-catenin and GSK-3ß, inhibited c-fos, PDX-1, and Bcl-2 expression, and enhanced cell apoptosis. The key findings of our study demonstrate that miR-128-3p aggravates cardiovascular calcification and IR in T2DM rats by downregulating ISL1 through the activation of the Wnt pathway. Thus, miR-128-3p may serve as a potential target for the treatment of T2DM.

A Non-Targeted Liquid Chromatographic-Mass Spectrometric Metabolomics Approach for Association with Coronary Artery Disease: An Identification of Biomarkers for Depiction of Underlying Biological Mechanisms.

BACKGROUND We performed non-targeted metabolomics analysis using liquid chromatography-mass spectrometry coupled technique to explore the biological mechanism of coronary artery disease (CAD) events for improved prediction. MATERIAL AND METHODS We studied the association of CAD events in 4092 individuals and observed the replication of sphingomyelin (28:1), lysophosphatidylcholine (18:2), lysophosphatidylcholine (18:1), and monoglyceride (18:2), which were independent of main CAD risk factors. RESULTS We found that these 4 metabolites were responsible for traditional risk factors and also contributed to the modifications related to reclassification and discrimination. Monoglycerides (MonoGs) were positively associated with C-reactive proteins and body mass index, while lysophosphatidylcholines (LPPCs), which had less evidence of subclinical CAD in an additional 1010 participants, yielded a reverse pattern. An association between monoGs and CAD independence of triglycerides (triGs) were also observed. On the basis of Mendelian randomization analysis, we observed a positive but weak irregular effect (odds ratio per unit increase in standard deviation in monoG=1.11, P-value=0.05) on CAD. CONCLUSIONS Our work establishes the relationship of metabolome with coronary artery disease and explains the biological mechanism of CAD events, as we identified the above-mentioned metabolites along with the evidence supporting their clinical use.

[Effect of Shexiang Baoxin pill on coronary vasodilation by analysis of coronary angiography].

OBJECTIVE: To evaluate the effect of Shexiang Baoxin Pill (SBP) on coronary vasodilation by analysis of coronary angiography (CAG). METHODS: A consecutive cohort of 300 patients who underwent CAG between January 2013 and July 2013 were recruited and randomly assigned to 2 groups before operation. Patients in the SBP group sublingually took SBP, while those in the control group sublingually took placebos. All patients repeatedly underwent CAG 5 min after administration. The vascular diameter was calculated by quantitative angiography analysis method. The diameter of the left anterior descending coronary artery was measured in patients whose coronary arteries had no stenosis. The narrowest vascular diameter was measured in patients whose coronary arteries had stenosis. The heart rate, blood pressure, and the vascular diameter were compared between before and after administration in the two groups. RESULTS: In the two groups, there was no significant difference in changes of heart rate, systolic pressure, or diastolic pressure between before and after administration (all P > 0.05). There were 64 patients with normal CAG in the two groups, 30 in the control group and 34 in the SBP group. CAG showed there were 236 patients with stenotic coronary artery, 110 in the control group and 126 in the SBP group. The vascular diameter was obviously larger in patients in the SBP group with normal or abnormal CAG after administration (all P < 0.01). It was also obviously larger than that of the control group after administration (P < 0.05, P < 0.01). CONCLUSION: SBP could dilate both normal coronary artery and lesioned coronary arteries, but did not lead to fastened heart rate and decreased blood pressure.

Circulating Serum Fatty Acid-Binding Protein 4 Levels Predict the Development of Diabetic Retinopathy in Type 2 Diabetic Patients.

PURPOSE: Fatty acid-binding protein 4 (FABP4) has been implicated in the pathology of diabetes and macrovascular diseases. Serum FABP4 levels were determined in type 2 diabetic patients without diabetic retinopathy (DR) at admission in order to investigate a possible contribution of FABP4 to the increased risk of 5-year incidence of DR. DESIGN: Cohort study. METHODS: A total of 738 patients with type 2 diabetes without DR were consecutively enrolled and followed up prospectively. Retinopathy evaluation was annually performed by ophthalmologists in the following 5 years. Multivariate analyses were performed using logistic regression models. RESULTS: During the follow-up period, 152 (20.60% [95% CI: 17.68%-23.51%]) patients developed DR and 60 (8.13% [95% CI: 6.16%-10.10%]) patients developed vision-threatening DR (VTDR). Nonparametric Spearman rank correlation revealed a statistically significant positive correlation between serum FABP 4 level and international Clinical Diabetic Retinopathy Severity Scales (r = 0.348; P < .001). After adjustment for other established risk factors, in multivariate models comparing the third and fourth quartiles against the first quartile of the FABP4, levels of FABP4 were associated with DR and the adjusted risk of DR increased by 124% (OR = 2.24 [95% CI 1.65-3.68], P = .006) and 227% (3.27 [2.04-5.56], P < .001), respectively. Similarly, the adjusted risk of VTDR increased by 140% (OR = 2.40 [95% CI 1.32-3.82], P = .001) and 278% (3.78 [2.17-6.59], P < .001), respectively. CONCLUSION: FABP4 shows potential as a novel biomarker for DR prediction in Chinese patients with T2DM, and strict glycemic control and more frequent retinal examination should be highlighted for T2DM patients with the highest quartile range of FABP4.

Lycium barbarum polysaccharide exhibits cardioprotection in an experimental model of ischemia-reperfusion damage.

Cardiovascular diseases are a major cause of mortality and disability worldwide. The present study investigated the cardio-protective effects of polysaccharides extracted from Lycium barbarum (LB), the fruit of which is traditionally used in Chinese medicine. Polysaccharides were characterized using Fourier transform infrared spectroscopy and high­performance liquid chromatography techniques. The present study demonstrated that LB polysaccharides are composed of glucose and fructose monosaccharides in a molar ratio of 1:2. A total of 36 rats were divided into three groups plus a control group, with nine animals in each group, and were used for studying the cardioprotective effects of LB polysaccharides. The low­dose group received 150 mg/kg body weight (BW) polysaccharides and the high­dose group received 300 mg/kg BW polysaccharides. The results demonstrated that the LB polysaccharides reduced the levels of myocardial lactate dehydrogenase and increased the sodium­potassium ATPase and calcium ATPase activities in rats with heart ischemia­reperfusion injury. In addition, there was a decrease in the myocardial Bax­positive expression and the rate of myocardial cell apoptosis, along with a dose­dependent increase in Bcl­2­positive expression. Therefore, it was concluded that LB polysaccharides are able to halt the progression of cardiovascular diseases.