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BACKGROUND@#The cardiomyocyte apoptosis is considered as one of major contributions to cardiac remodeling after myocardial infarction (MI). Numerous studies find that circular RNAs (circRNAs) play pivotal roles in a variety of biological functions. However, the role of circ_0068655 in MI and human induced pluripotent stem-derived cardiomyocytes (HCMs) remains unknown. @*METHODS@#The expression of circ_0068655, miR-498, and PRKC apoptosis WT1 regulator (PAWR) in human MI heart tissues and hypoxia subjected HCMs was evaluated with qRT-PCR and Western blot. The effects of circ_0068655 on hypoxia-induced apoptotic death and cell migration in HCMs were evaluated with qRT-PCR, cell viability, cell death ELISA (POD), and Caspase-3 activity assay, and Trans-well assay, respectively. Furthermore, luciferase assay, qRT-PCR, biotin-labeled miRNA pulldown assay, and Western blot were employed in the functional studies. @*RESULTS@#We found that the expression of circ_0068655 and PAWR was enhanced in MI patients and hypoxia subjected HCMs; by contrast, the expression of miR-498 decreased. Inhibited expression of circ_0068655 in HMCs counteracted hypoxia-induced apoptotic death and impaired cell migration, in sharp contrast to circ_0068655 knockdown. We identified that circ_0068655 sponged an endogenous miR-498 to sequester and inhibit its activity, leading to the increased PAWR expression. @*CONCLUSIONS@#Our findings reveal that the expression of circ_0068655 can promote cardiomyocyte apoptosis through the modulation of miR-498-PAWR axis in vitro, which highlights the diagnostic and therapeutic value of circ_0068655 in patients with MI.
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BACKGROUND@#The cardiomyocyte apoptosis is considered as one of major contributions to cardiac remodeling after myocardial infarction (MI). Numerous studies find that circular RNAs (circRNAs) play pivotal roles in a variety of biological functions. However, the role of circ_0068655 in MI and human induced pluripotent stem-derived cardiomyocytes (HCMs) remains unknown. @*METHODS@#The expression of circ_0068655, miR-498, and PRKC apoptosis WT1 regulator (PAWR) in human MI heart tissues and hypoxia subjected HCMs was evaluated with qRT-PCR and Western blot. The effects of circ_0068655 on hypoxia-induced apoptotic death and cell migration in HCMs were evaluated with qRT-PCR, cell viability, cell death ELISA (POD), and Caspase-3 activity assay, and Trans-well assay, respectively. Furthermore, luciferase assay, qRT-PCR, biotin-labeled miRNA pulldown assay, and Western blot were employed in the functional studies. @*RESULTS@#We found that the expression of circ_0068655 and PAWR was enhanced in MI patients and hypoxia subjected HCMs; by contrast, the expression of miR-498 decreased. Inhibited expression of circ_0068655 in HMCs counteracted hypoxia-induced apoptotic death and impaired cell migration, in sharp contrast to circ_0068655 knockdown. We identified that circ_0068655 sponged an endogenous miR-498 to sequester and inhibit its activity, leading to the increased PAWR expression. @*CONCLUSIONS@#Our findings reveal that the expression of circ_0068655 can promote cardiomyocyte apoptosis through the modulation of miR-498-PAWR axis in vitro, which highlights the diagnostic and therapeutic value of circ_0068655 in patients with MI.
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Objective To compare the effects of different right ventricular pacing sites on left ventricle systolic function in elderly patients with sick sinus syndrome (SSS).Methods A total of 78 elderly patients with SSS were selected in our hospital from 2014 to 2016,and were divided into the right ventricular apical group (RVA group,40 cases) and right ventricular outflow tract group (RVOT group,38 cases) according to sites of right ventrieular pacing.The QRS duration,accumulative total right ventricular pacing percentage and left ventricle function indicators were compared between the two groups before operation and 3,9 months after operation.Results There was no statistically significant difference in QRS duration and left ventricle function indicators before operation between the two groups (P＞0.05).The QRS durations in the RVA group at 3,9 months after operation were longer than those in the RVOT group,there were statistically significant differences (P＜0.05).No statistically significant difference was found in accumulative total right ventricular pacing percentage at 9 months after operation between the two groups (P＞ 0.05).At 9 months after operation,the left ventricular ejection fraction in the RVOT group was higher than that in the RVA group,and the left ventricular end diastolic diameter was lower than that in the RVA group,there were statistically significant differences (P＜0.05).Conclusion The effects of RVOT pacing on left ventricle systolic function in elderly patients with SSS is superior to the RVA pacing.
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Objective To compare the effects of different right ventricular pacing sites on left ventricle systolic function in elderly patients with sick sinus syndrome (SSS).Methods A total of 78 elderly patients with SSS were selected in our hospital from 2014 to 2016,and were divided into the right ventricular apical group (RVA group,40 cases) and right ventricular outflow tract group (RVOT group,38 cases) according to sites of right ventrieular pacing.The QRS duration,accumulative total right ventricular pacing percentage and left ventricle function indicators were compared between the two groups before operation and 3,9 months after operation.Results There was no statistically significant difference in QRS duration and left ventricle function indicators before operation between the two groups (P＞0.05).The QRS durations in the RVA group at 3,9 months after operation were longer than those in the RVOT group,there were statistically significant differences (P＜0.05).No statistically significant difference was found in accumulative total right ventricular pacing percentage at 9 months after operation between the two groups (P＞ 0.05).At 9 months after operation,the left ventricular ejection fraction in the RVOT group was higher than that in the RVA group,and the left ventricular end diastolic diameter was lower than that in the RVA group,there were statistically significant differences (P＜0.05).Conclusion The effects of RVOT pacing on left ventricle systolic function in elderly patients with SSS is superior to the RVA pacing.
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Objective To compare the curative effect and safety of non-X-ray fluoroscopic radiofrequency catheter ablation and conventional X-ray fluoroscopic radiofrequency catheter ablation in treating paroxysmal supraventricular tachycardia by Ensite Velocity three-dimensional electroanatomical mapping system.Methods One hundred cases diagnosed as paroxysmal supraventricular tachycardia in this hospital during 2014-2016 were selected and randomly divided into the control group (conventional X-ray exposure) and the experimental group(non-X-ray exposure by three-dimensional electroanatomical mapping system),50 cases in each group.The operation time,X-ray exposure time,complication rate,immediate and follow-up success rate were compared between two groups.Results There was no statistically significant difference in the operation time between the two groups (P＞0.05),but the X-ray exposure time in the experimental group [(0.46±0.14) min] was significantly lower than that of the control group [(13.87 ±4.03) min] and the complication rate (0 ％) was also significantly lower than that of the control group (8.00％);the immediate success rate (98.00 ％) was significantly was significantly decreased compared with the control group[(0.46± 0.14)min vs.(13.87 ±4.03)min],the complication rate was significantly lower than that in the control group(0 ％ vs.8 ％),the immediate success rate was significantly higher than that in the control group(98.00 ％ vs.84.00 ％),the follow up success rate was also significantly higher than that in the control group (94.00 ％ vs.74.00 ％),the differences were statistically significant (P＜0.05).Conclusion Using Ensite Velocity three-dimensional electroanatomical mapping system to conduct radiofrequency catheter ablation has an ideal clinical effect in the treatment of paroxysmal supraventricular tachycardia,which is safe and reliable.
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Calcium/calmodulin-dependent protein kinaseⅡ (CaMKⅡ) has multiple functions, which made it play a central role in cardiovascular disease. Especially it activates numerous downstream targets in various signaling pathways that promotes vascular disease, heart failure, myocardial hypertrophy and arrhythmias. CaMKⅡcan impact calcium balance and increase calcium leak in myocardial cell via phosphorylating L type calcium channel, Ryanodine receptor (RyR 2) and phos?pholamban (PLN), and regulate ATP sensitive potassium current (IKATP) and late sodium current by affecting sodium channels and potassium channels. In addition, It can directly regulate transcription via activating the silk crack the original activated protein kinases (MAPKs) and acetylation enzyme (HDAC). These mechanisms have important roles in myocardial hypertro?phy, heart failure and arrhythmia. So we focus to demonstrating the structure and action mechanism of CaMKⅡto improve a new therapy of cardiovascular disease.
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BACKGROUND:Our prior experiments have confirmed that 10 μmol/L oxytocin can induce transformation of bone marrow mesenchymal stem cels into myocardial cels. OBJECTIVE: To investigate the effects of Ginsenoside Rh2 on oxytocin-induced transformation of bone marrow mesenchymal stem cels into myocardial cels. METHODS:Rat bone marrow mesenchymal stem cels were isolated by differential adherence method. These isolated cels were randomly divided into five groups. In the blank control group, cels were routinely cultured. In the oxytocin group, cels were cultured with 10 μmol/L oxytocin for 2 consecutive weeks. In the Ginsenoside Rh2 low-, middle-, and high-dose groups, cels were treated with 0.5, 1, 2 μmol/L Ginsenoside Rh2respectively for 24 hours and then with oxytocin for additional 2 consecutive weeks. RESULTS AND CONCLUSION: Optical microscopy showed that compared to the blank control group, some cels in the oxytocin group exhibited an increased soma and some cels grew in clusters and the cel clusters enlarged with the increase in Ginsenoside Rh2 dose. Immunocytochemical staining and western blot analysis showed that cardiac Troponin T and connexin 43 protein expression in the oxytocin, Ginsenoside Rh2 low-, middle-, and high-dose groups were significantly greater than in the blank control group (P < 0.05), and cardiac Troponin T and connexin 43 protein expression in the Ginsenoside Rh2 groups was increased with the increase in Ginsenoside Rh2 dose and was significantly higher than that in the oxytocin group (P < 0.05). Confocal laser scanning microscopy showed that the relative fluorescence intensity of free calcium in the bone marrow mesenchymal stem cels in the oxytocin group was significantly increased after induction by oxytocin for 2 weeks (P < 0.05), while the relative fluorescence intensity in the Ginsenoside Rh2 groups was significantly higher than that in the Ginsenoside Rh2 groups and was positively correlated with the dose of Ginsenoside Rh2. These findings suggest that Ginsenoside Rh2 can obviously promote oxytocin-induced transformation of bone marrow mesenchymal stem cels into myocardial celsin vitro.
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Cardiac contractile dysfunction and arrhythmic genesis are resulted from disturbed intracellular Na+and Ca2+ handling under condition of oxidation stress. Stress-induced intracellular signaling regulated mechanisms in which many activated stress kinases, such as cAMP-dependent protein kinase A, protein kinase C , Ca/calmodulin-dependent pro-tein kinaseⅡand classical pathways, are known to be involved. However, it is becoming increasingly evident that reactive oxygen species may directly oxidize these kinases, Na+and Ca2+channel protein and transporters, which lead to changing of intracellular Na+and Ca2+accumulation, and to trigger of arrhythmias.
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Objective To investigate the variation of the thioredoxin system (Trx),and the role of it in transient out-ward potassium current (Ito) channels in left ventricular myocytes of diabetes mellitus (DM) in rats. Methods Forty-five SD rats were divided into DM group and control group. DM group were treated with streptozotocin (STZ) to induce DM model. The values of left ventricular end diastolic diameter (LVEDD), end-systolic diameter (LVESD), fractional shortening (LVFS), ejection fraction (LVEF) and heart rate (HR), QRS duration and corrected QT (QTc) interval were detected by echocardiogra-phy (UCG) and electrocardiogram (ECG) in two groups. The left ventricular myocardial tissue samples were taken to detect the Trx,glutaredoxin (GRX),thioredoxin reductase (TrxR) and glutathione reductase (GR) by using UV spectrophotometer. The level of free thiol (P-SH) of total cardiac protein was detected by 5, 5′-dithio-bis-2-nitrobenzoic acid method. Ito of the cardiomyocytes was recorded by whole-cell patch-clamp method. After being incubated in vitro with insulin(Ins), treated with TrxR inhibitor-auranofin(AF) and 13-cis-retinoic acid(RA), the changes of Ito of the cardiomyocytes were observed. Results Compared with control group, the values of heart rate (HR), left ventricular minor axis decurtaion rate (LVFS), left ventricular ejection fraction (LVEF) and TrxR were lower in DM group. The values of LVEDD, LVESD, QRS and QTc inter-vals, Trx, Grx and P-SH were higher in DM group than those of control group. Ito density was significantly higher in DM+Ins group than that of DM group, Ins+RA group and Ins+AF group when the stimulation voltage ≥ 0 mV (P ＜ 0.05). Conclusion The impaired Trx system in diabetic rat myocardium was the electrophysiological basis of the reduced ventric-ular function and arrhythmia. And Ins was able to reverse the decreased Ito of cardiomyocytes in DM rats.
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Morphine antagonist naloxone (3mg/kgiv ) induced a rise in blood pressure,pulse pressure & respiratory rate in the rat under hemorrhagic shock. It also improved the survival rate. ?Receptor antagonist pheno-xybenzamine ( 1 mg/kg iv ) or adrenalectomy abolished the beneficial effects of naloxone. Reserpine ( 1 mg/kg ip for 5 d) which depleted catecholamines of periphal sympathetic nervous system could not abolish naloxone effects. Resrpine plus adrenalectomy abolished naloxone actions again. It is suggested that the effect of naloxone on the blood pressure is mainly due to release of catecholamine from adrenalmedu-llary. The results of isolated adrenal perfusion indicated that naloxone could not induce a rise in catecholamine concentration of perfused liquid. It is suggested that the action of naloxone on catecholamine release may not be a result of direct action upontbe chromaffin cells.