Ning Ye

Early repolarization pattern in the general population: Prevalence and associated factors

OBJECTIVES To evaluate the prevalence of early repolarization pattern (ERP) in the general rural Chinese population and identify the contributing risk factors. METHODS A cross-sectional study of 11,956 permanent residents of Liaoning Province ≥35y of age was conducted between January and August 2013 (response rate 85.3%). ERP was diagnosed if there was J-point elevation of ≥0.1mV in ≥2 leads in the inferior (II, III, aVF) or lateral (I, aVL, V4-6) territory, or both. Risk factors for ERP were evaluated with a stepwise logistic regression analysis. RESULTS The overall prevalence of ERP was 1.3%, and it was higher in men than women (2.6 vs. 0.2%, P<0.001), decreasing with increasing age. Percent of ERP positive in lateral leads, inferior, and both was 73.0%, 15.3%, and 11.7%, respectively. Stepwise logistic regression demonstrated that independent clinical factors for ERP included age (odds ratio [OR] 0.68; P<0.001), male sex (OR 17.09; P<0.001), systolic blood pressure (SBP) (OR 0.77; P=0.022), stroke (OR 0.14; P=0.055), RR interval (OR 1.27; P=0.001), QTc interval (OR 0.76; P=0.008), QRS duration (OR 0.67; P=0.001), Cornell voltage (OR 0.28; P<0.001), and Sokolow-Lyon voltage (OR 2.03; P<0.001). CONCLUSIONS Although the prevalence of ERP in general rural Chinese population is low, younger age, male sex, lower SBP, non-stroke history, longer RR interval, shorter QTc interval, shorter QRS duration, lower Cornell voltage, and higher Sokolow-Lyon voltage are independent risk factors.

The Protective Role of the TOPK/PBK Pathway in Myocardial Ischemia/Reperfusion and H2O2-Induced Injury in H9C2 Cardiomyocytes

T-LAK-cell-originated protein kinase (TOPK) is a PDZ-binding kinase (PBK) that was recently identified as a novel member of the mitogen-activated protein kinase (MAPK) family. It has been shown to play an important role in many cellular functions. However, its role in cardiac function remains unclear. Thus, we have herein explored the biological function of TOPK in myocardial ischemia/reperfusion (I/R) and oxidative stress injury in H9C2 cardiomyocytes. I/R and ischemic preconditioning (IPC) were induced in rats by 3-hour reperfusion after 30-min occlusion of the left anterior descending coronary artery and by 3 cycles of 5-min I/R. Hydrogen peroxide (H2O2) was used to induce oxidative stress in H9C2 cardiomyocytes. TOPK expression was analyzed by western blotting, RT-PCR, immunohistochemical staining, and immunofluorescence imaging studies. The effects of TOPK gene overexpression and its inhibition via its inhibitor HI-TOPK-032 on cell viability and Bcl-2, Bax, ERK1/2, and p-ERK1/2 protein expression were analyzed by MTS assay and western blotting, respectively. The results showed that IPC alleviated myocardial I/R injury and induced TOPK activation. Furthermore, H2O2 induced TOPK phosphorylation in a time-dependent manner. Interestingly, TOPK inhibition aggravated the H2O2-induced oxidative stress injury in myocardiocytes, whereas overexpression relieved it. In addition, the ERK pathway was positively regulated by TOPK signaling. In conclusion, our results indicate that TOPK might mediate a novel survival signal in myocardial I/R, and that its effect on anti-oxidative stress involves the ERK signaling pathway.

Diabetes mellitus is an independent risk factor for atrial fibrillation in a general Chinese population

To explore the association between atrial fibrillation (AF) and diabetes mellitus in a general Chinese population, and the influence of hypertension.

Advanced glycation end products promote the proliferation and migration of primary rat vascular smooth muscle cells via the upregulation of BAG3

The present study was aimed to investigate the role of reactive oxygen species (ROS) on advanced glycation end product (AGE)-induced proliferation and migration of vascular smooth muscle cells (VSMCs) and whether Bcl-2-associated athanogene 3 (BAG3) is involved in the process. Primary rat VSMCs were extracted and cultured in vitro. Cell viability was detected by MTT assay and cell proliferation was detected by EdU incorporation assay. Cell migration was detected by wound healing and Transwell assays. BAG3 was detected using qPCR and western blot analysis. Transcriptional and translational inhibitors (actinomycin D and cycloheximide, respectively) were used to study the effect of AGEs on the expression of BAG3 in VSMCs. Lentiviral plasmids containing short hairpin RNA (shRNA) against rat BAG3 or control shRNA were transduced into VSMCs. Cellular ROS were detected by 2′,7′-dichlorofluorescein diacetate (DCFH-DA) staining. Mitochondrial membrane potential was detected by tetramethylrhodamine methyl ester (TMRE) staining. AGEs significantly increased the expression of BAG3 in a dose-and time-dependent manner. Furthermore, AGEs mainly increased the expression of BAG3 mRNA by increasing the RNA synthesis rather than inhibiting the RNA translation. BAG3 knockdown reduced the proliferation and migration of VSMCs induced by AGEs. BAG3 knockdown reduced the generation of ROS and sustained the mitochondrial membrane potential of VSMCs. Reduction of ROS production by N-acetylcysteine (NAC), a potent antioxidant, also reduced the proliferation and migration of VSMCs. On the whole, the present study demonstrated for the first time that AGEs could increase ROS production and promote the proliferation and migration of VSMCs by upregulating BAG3 expression. This study indicated that BAG3 should be considered as a potential target for the prevention and/or treatment of vascular complications of diabetes.

Assessment of novel Peguero-Lo Presti electrocardiographic left ventricular hypertrophy criteria in a large Asian population: Newer may not be better

BACKGROUND Recently, the novel Peguero-Lo Presti electrocardiographic criteria to diagnose left ventricular hypertrophy (LVH) were developed from Caucasian American population with a relatively high sensitivity. However, further validation on a large Asian population has never been conducted. Thus, this study was to test and validate the overall performance of this index in a general population from China. METHODS A total of 10,614 permanent residents ≥35 years of age were included in this study. All participants completed 12-lead electrocardiography and echocardiography at the same visit. A receiver-operating characteristic curve was used for comparing the performance of electrocardiographic indices in diagnosing echocardiographic LVH. RESULTS The Peguero-Lo Presti criteria had higher sensitivity but lower specificity than Cornell and Sokolow-Lyon voltage according to the recommended criteria. The area under the curve of this novel Peguero-Lo Presti voltage was lower than that of Cornell for predicting LVH defined by both left ventricular mass/body surface area (0.665 vs 0.699 in males; 0.689 vs 0.721 in females) and left ventricular mass/height2.7 (0.623 vs 0.681 in males; 0.642 vs 0.709 in females) (all Ps < 0.05). By changing cutoff values, Cornell voltage outperformed Peguero-Lo Presti whether to achieve a relatively high sensitivity or specificity. CONCLUSIONS The novel Peguero-Lo Presti voltage may not be a better screening tool for LVH in Asian population. In comparison with this new index, Cornell voltage could be a better screening test for LVH by changing its cutoff values to obtain maximum sensitivity.

Advanced Glycation End Products Inhibit the Proliferation of Human Umbilical Vein Endothelial Cells by Inhibiting Cathepsin D

We aimed to investigate the effect of advanced glycation end products (AGEs) on the proliferation and migration ability of human umbilical vein endothelial cells (HUVECs). Cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) assay, real-time cell analyzer and 5-Ethynyl-2′-deoxyuridine (EdU) staining. Cell migration was detected by wound-healing and transwell assay. AGEs significantly inhibited the proliferation and migration of HUVECs in a time-and dose-dependent way. Western blotting revealed that AGEs dramatically increased the expression of microtubule-associated protein 1 light chain 3 (LC3) II/I and p62. Immunofluorescence of p62 and acridine orange staining revealed that AGEs significantly increased the expression of p62 and the accumulation of autophagic vacuoles, respectively. Chloroquine (CQ) could further promote the expression of LC3 II/I and p62, increase the accumulation of autophagic vacuoles and promote cell injury induced by AGEs. In addition, AGEs reduced cathepsin D (CTSD) expression in a time-dependent way. Overexpression of wild-type CTSD significantly decreased the ratio of LC 3 II/I as well as p62 accumulation induced by AGEs, but overexpression of catalytically inactive mutant CTSD had no such effects. Only overexpression of wild-type CTSD could restore the proliferation of HUVECs inhibited by AGEs. However, overexpression of both wild-type CTSD and catalytically inactive mutant CTSD could promote the migration of HUVECs inhibited by AGEs. Collectively, our study found that AGEs inhibited the proliferation and migration in HUVECs and promoted autophagic flux, which in turn played a protective role against AGEs-induced cell injury. CTSD, in need of its catalytic activity, may promote proliferation in AGEs-treated HUVECs independent of the autophagy-lysosome pathway. Meanwhile, CTSD could improve the migration of AGEs-treated HUVECs regardless of its enzymatic activity.

Atorvastatin protects the proliferative ability of human umbilical vein endothelial cells inhibited by angiotensin II by changing mitochondrial energy metabolism

This study aimed to explore whether angiotensin II (Ang II) inhibits the proliferation of human umbilical vein endothelial cells (HUVECs) by changing mitochondrial energy metabolism, and whether atorvastatin has a protective role via restoration of endothelial function. HUVECs were treated with 1 µM Ang II alone or with 10 µM atorvastatin for 24 h. Proliferation was detected by MTT assay, cell counting, 5-ethynyl-2′-deoxyuridine assay and real-time cell analyzer. Mitochondrial energy metabolism including oxygen consumption rate and extracellular acidification rate were measured using a Seahorse metabolic flux analyzer. Mitochondrial membrane potential was detected under fluorescence microscope following staining with tetramethylrhodamine. Respiratory chain complexes I–V were detected using western blotting. The current study showed that Ang II inhibits the proliferation of HUVECs. Results from the Seahorse metabolic flux analyzer indicated that Ang II decreased basal oxygen consumption, maximal respiration capacity, spare respiration capacity, adenosine triphosphate-linked respiration and non-mitochondrial respiration. By contrast, Ang II increased the proton leak. Additionally, Ang II increased glycolysis, glycolytic capacity and non-glycolytic acidification. Furthermore, these effects were all suppressed by atorvastatin. The results indicated that atorvastatin prevents cellular energy metabolism switching from oxidative phosphorylation to glycolysis induced by Ang II and protected the proliferative ability of HUVECs.