LncRNA ZEB1-AS1 knockdown alleviates oxidative low-density lipoprotein-induced endothelial cell injury via the miR-590-5p/HDAC9 axis.

Oxidative low-density lipoprotein (ox-LDL) is thought to induce vascular endothelial cell injury, which contributes to the aetiopathogenesis of atherosclerosis (AS). Several previous reports have identified that lncRNA ZEB1-AS1 participates in the regulatory mechanisms of endothelial cell injury, but the potential interaction mechanism between ZEB1-AS1 and miR-590-5p in ox-LDL-induced endothelial cell damage is not clear. ZEB1-AS1 and miR-590-5p expression were tested by quantitative real-time polymerase chain reaction (qRT-PCR) in ox-LDL-treated endothelial cells. The proliferation and apoptosis were determined by MTT and Annexin V/PI double-staining assay, respectively. The protein expression of HDAC9, tumor necrosis factor α (TNF-α), cleaved caspase-3, and cleaved PARP were measured by western blot analysis. Dual-luciferase reporter and RIP assays affirmed the functional targets of ZEB1-AS1. ZEB1-AS1 expression was upregulated in ox-LDL-treated HUVECs, and miR-590-5p was lessened in a dose- or time-depended manner, respectively. Knockdown of ZEB1-AS1 facilitated ox-LDL-treated endothelial cell proliferation and inhibited cell apoptosis. Moreover, miR-590-5p was directly targeted via ZEB1-AS1 in ox-LDL-treated HUVECs. ZEB1-AS1 silencing attenuated ox-LDL-induced cell injury via regulation of miR-590-5p expression. Furthermore, HDAC9 reversed the influence of miR-590-5p on propagation and apoptosis of ox-LDL-induced endothelial cells. Knockdown of ZEB1-AS1 alleviates ox-LDL-induced endothelial cell injury by regulating the miR-590-5p/HDAC9 axis.

Ebselen protects rat hearts against myocardial ischemia-reperfusion injury.

Ebselen is an organoselenium compound that has demonstrated potent antioxidant and anti-inflammatory effects in previous studies. The present study was conducted to evaluate the effect of ebselen on myocardial ischemia-reperfusion (I/R) injury in a rat model and to elucidate the related mechanisms. Myocardial infarct size was assessed using triphenyltetrazolium chloride staining. Myocardial injury was evaluated according to the histopathological and ultrastructural alterations of rat hearts and the serum activity levels of cardiac enzymes, including creatine kinase (CK), CK-MB isoenzyme and lactate dehydrogenase (LDH). Cardiomyocyte apoptosis was detected using the terminal dUTP nick end-labelling (TUNEL) assay. In addition, the expression of apoptosis-associated proteins was measured using western blot analysis. In heart tissue specimens the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and levels of malondialdehyde (MDA) and protein carbonyl (PC) were also detected. The results indicated that ebselen reduced I/R-induced increase in myocardial infarct size and prevented the I/R-induced decreases in ejection fraction and fractional shortening. Further of note, ebselen improved I/R-induced rat heart injury. This was indicated by attenuation of histological and ultrastructural changes; reduction of serum CK, CK-MB and LDH activity levels; and decreased cell apoptosis on TUNEL staining, which was verified by decreased expression of cleaved (C)-Caspase-8, C-Caspase-3, B-cell lymphoma 2 (Bcl-2)-associated X protein and C-PARP, and increased expression of Bcl-2. Additionally, SOD and GPx activity levels were significantly higher, while MDA and PC levels were significantly lower in the ebselen + I/R group compared with in the I/R group. In conclusion, the present results suggested that ebselen serves an important role in protecting against myocardial I/R injury. The underlying mechanism may involve suppression of cardiomyocyte apoptosis and promotion of antioxidant activity.

Assessment of RANTES levels as the indicators of plaque vulnerability in rabbit models of atherosclerosis.

The aim of the present study was to determine the chemokine RANTES (regulated on activation, normal T-cell expressed, and secreted) levels in plasma and atherosclerotic plaques and to assess their diagnostic efficacy in the evaluation of vulnerable plaques. The rabbit models of vulnerable atherosclerotic plaque (VAP) were established by high fat diet and pharmaceutical triggering. The serum RANTES levels of VAP group (91.97 ± 8.51 ng/ml) were significantly higher than those of AS (atherosclerosis) group (50.03 ± 2.92 ng/ml). Consistently, the mRNA and protein of RANTES in vulnerable atherosclerotic plaques were also obviously up-regulated compared to AS group (P < 0.01). Moreover, corrected plaque area and vulnerability index of VAP group proved to be significantly higher than AS group. The correlation coefficient between RANTES and plaque vulnerability indicated that RANTES, especially plaque RANTES, was positively correlated with VAP. In addition, increased expression of nuclear factor kappa B p65 (NF-κB p65) was observed in VAP group compared to AS group (P < 0.05), which partly accounted for the increased RANTES levels. In conclusion, positive associations between RANTES and plaque vulnerability suggest that higher RANTES levels may be associated with atherosclerosis and high-risk plaques. Our study highlights the utility of both serum and plaque RANTES levels as indicators of plaque vulnerability in the field of preventive cardiology.

Significance of CAVI, hs-CRP and homocysteine in subclinical arteriosclerosis among a healthy population in China.

PURPOSE: The purpose of this study is to evaluate the ability of cardio-ankle vascular index (CAVI), high-sensitivity C-reactive protein (hs-CRP) levels and homocysteine (Hcy) levels to screen for subclinical arteriosclerosis (subAs) in an apparently healthy population, with the view to obtaining an optimal diagnostic marker or profile for subAs. METHODS: Subjects (152) undergoing routine health examinations were recruited and divided into two groups: carotid arteriosclerosis (CA) and non-carotid arteriosclerosis (NCA), according to carotid intima-media thickness (CMIT). CAVI was calculated based on blood pressure and pulse wave velocity. Serum hs-CRP and Hcy levels were also measured. A Receiver Operating Characteristic (ROC) curve was plotted to evaluate the efficacy of each in carotid arteriosclerosis screening. Ten parameter combinations, designated W1 to W10, were compared in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: The levels of all three parameters were significantly higher in the CA group, compared with the NCA group. ROC curves showed that the area under the curve (AUC) for CAVI was 0.708 (95%CI: 0.615-0.800), which is significantly larger than that of either hs-CRP (0.622) or Hcy (0.630), respectively (P < 0.001). Maximum sensitivity (100%) and NPV (100%) were attained with W10, while maximum specificity (86.2%) and PPV (46.7%) were obtained with W7. With W9, the maximum Youden index (0.416) was obtained, with a sensitivity of 77.8% and specificity of 63.8%. CONCLUSIONS: CAVI is more effective than hs-CRP or Hcy for subAs screening. The optimal profile was obtained with a combination of CAVI and other parameters.

One-year clinical outcome of a randomized trial of polymer-free paclitaxel-eluting stents versus biodegradable polymer-based rapamycin-eluting stents in patients with coronary heart disease.

BACKGROUND: More widespread use of drug-eluting stents (DES) to treat coronary heart disease (CHD) has recently generated more attention to thrombosis, which was relative to the polymer. Polymer-free and biodegradable polymer-based stents are more frequently studied, but their efficacy on preventing detrimental clinical events is unclear. METHODS AND RESULTS: To assess whether polymer-free paclitaxel-eluting stent (YINYI stent) was noninferior or equivalent to biodegradable polymer-based rapamycin-eluting stents (EXCEL stent) in preventing detrimental clinical cardiovascular events, a total of 167 consecutive CHD patients requiring DES implantation were randomly divided into the YINYI group (n = 82) and the EXCEL group (n = 85). The primary end-point was major adverse cardiac events (MACE). The secondary end-points included stent thrombosis events, all-cause mortality, and rehospitalization. The study was designed to test the noninferiority or equivalence of the YINYI stent compared with the EXCEL stent with respect to one-year MACE according to a noninferiority or equivalence margin of 0.1. One-year MACE was 6.10% in the YINYI group versus 5.88% in the EXCEL group. The lower limit of the one-sided 95% confidence interval was -0.0582 (P = 0.002 from the test for noninferiority). The 95% confidence interval for the equivalence test was [-0.0698, 0.0742] (P1 =0.004 and P2 =0.007 from 2 times the 1-sided test for equivalence). There was no statistically significant difference in thrombosis events, all-cause death, and rehospitalization (all P > 0.05). CONCLUSIONS: In this small randomized trial, polymer-free paclitaxel-eluting stents appear to be noninferior or equivalent to biodegradable polymer-based rapamycin-eluting stents.