1.Embryonic stem cell differentiation towards cardiomyocytes and its application in cardiac tissue engineering
Chinese Journal of Tissue Engineering Research 2007;0(34):-
Embryonic stem cells (ESCs) show potential prospect of wide application in establishing cardiac pharmacological model system, forming three-dimensional cardiac tissues and constructing biological pacemaker. The process of ESCs differentiating into cardiomyocytes is to simulate heart growth and development in vitro. The cases of transplanting ESCs into animal models confirm that the cardiac function is improved. Moreover, the research and exploitation of tissue engineered cardiac muscle tissue with vessel system brings hope for clinical cardiac muscle restoration. ESC-derived pacemaker can functionally integrate with quiescent ventricular muscle cells to induce rhythmic electrical and contractile activities in vitro. However, the immunological rejection limits its clinical application. Although ESCs have strong differentiation potential, the problems such as the differentiation process towards cardiomyocytes, ESC induction and signal regulatory pathway, and whether induced cardiomyocytes can substitute in vivo cardiomyocytes still need exploration.
2.ELECTROPHYSIOLOGICAL MECHANISM OF ATRIAL FIBRILLATION INDUCED BY ACETYLCHOLINE IN DOGS
Shaoping LU ; Riying DU ; Qiangsun ZHENG
Medical Journal of Chinese People's Liberation Army 2001;0(08):-
To study the electrophysiological mechanism of atrial fibrillation induced by acetylcholine(Ach). The results showed that:①Ach decreased ERP of four atrial sites.When the concentration of Ach was incseased, ERP of 4 sites became shorter but COVERP became bigger.②As the concentration of Ach was increased, the percent of AF induced by Ach and AF was increased with the duration prolonged( P 0 05).③There was a significant correlation between atrial vulnerability with ERP and COVERP( P
3.Experimental study on the synergistic action of retinol on leukemia inhibitory factor (LIF) maintaining undifferentiated state of murine embryonic stem cells
Jingjing GUO ; Qiangsun ZHENG ; Hongtao WANG
Medical Journal of Chinese People's Liberation Army 1981;0(04):-
Objective To investigate the synergistic effect of retinol and leukemia inhibitory factor (LIF) on maintaining pluripotency of murine embryonic stem cells (mESCs). Methods The mESCs were randomly divided into two groups, and they were all cultured with the same LIF concentration (100U/ml). Retinol was added into mESCs medium in experimental group, and retinol was not added in control group. 14 days after culturing, the changes in cell morphology were observed under an inverted microscope with alkaline phosphatase staining. The mRNA expression of Oct4 and Nanog was analyzed by RT-PCR, and the proteins for Oct4 and Nanog were determined by Western-blot for the assessment of the pluripotency of mESCs. Results 14 days after culturing, 78% of mESCs in the experimental group formed good cell colonies with good stereoscopic appearance, and they showed strong alkaline phosphatase (AKP) staining. While in the control group, only 35% of mESCs were in undifferentiated mode, and the cells were weakly positive with AKP staining. The quantity of undifferentiated mESCs in experimental group (7.02?0.34) was higher than that in control group (4.28?0.37, P
4.Reaction of human plasma nerve growth factor to radiofrequency catheter ablation
Shaoping LU ; Qiangsun ZHENG ; Ye YANG ; Lianru GAO ; Yanling TANG
Chinese Journal of Tissue Engineering Research 2006;10(45):187-189
BACKGROUND: Radiofrequency catheter ablation (RFCA) in dog triggers myocardial nerve sprouting and sympathetic hyperinnevation. It is possible that RFCA in humans has the same effect. Nerve growth factor (NGF) is a neurons nurture that supports the survival and differentiation of sympathetic neurons and enhances target innervation. Therefore, it is hypothetic that RFCA can increases plasma NGF concentration in humans.OBJECTIVE: To test the hypothesis that RFCA increases plasma NGF concentration in humans.DESIGN: Self-control experiment.SETTING: Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University of Chinese PLA.PARTICIPANTS: Forty-three patients were selected from the Cardiological Department of Tangdu Hospital, the Fourth Military Medical University of Chinese PLA from January to June 2005, including atrioventricular nodal reentrant tachycardia (AVNRT) (n=18), right-sided accessory pathways (RSAP) (n=13) and left-sided accessory pathways (LSAP) (n=12), 20 males and 23 females, ages 28-65 years, all agreed to participate in the study voluntarily.METHODS: Blood samples were obtained from the peripheral veins before ablation and at 6 hours, 1, 3, 5, 7 days after ablation. The plasma concentration of NGF was determined with enzyme-linked immunosorbent assay (ELISA).MAIN OUTCOME MEASURES: The plasma concentration of NGF was determined with ELISA before RFCA and at 6 hours, 1, 3, 5, 7 days after RFCA in each patient.RESULTS: Total 43 patients who were referred for ablation therapy for AVNRT, RSAP and LSAP were involved in the result analysis without loss. Plasma NGF increased at 6 hours after RFCA. Increased NGF continued to 7 days in the RFCA treated patients. The plasma NGF concentrations at 6 hours, 1, 3, 5, 7 days after RFCA in AVNRT, RSAP and LSAP ablations treated patients were (29.72±7.04), (30.94±5.68),(31.39 ±4.92), (31.06 ±4.56), (29.11 ±4.59), (31.77 ±6.25), (30.69 ±5.10),(31.46±4.96), (30.15±4.01), (30.43±3.14), (31.42±6.75), (31.00±5.20),(32.08±4.62), (30.67±3.71), (29.27±2.75) μg/L, respectively, and all more than that before RFCA [(14.89±2.84), (15.00±2.71), (15.51±2.75) μg/L, P < 0.01]. However, there were no significant differences in the NGF levels at 6 hours, 1, 3, 5 and 7 days after RFCA (P > 0.05). The plasma NGF concentration was not significant different among AVNRT, RSAP and LSAP ablation patients at any given time (P > 0.05). The number of RFCA applications, the procedure time and the total energy have no correlation with NGF concentration at any given time instance.CONCLUSION: RFCA increases plasma NGF concentration in humans and lasts for at least 7 days. The number of RFCA applications, the procedure time and the total energy have no correlation with NGF concentration at any given time instance.
5.Role of Transforming Growth Factor-?_1/Smad Pathway in the Collagen Synthesis of Cardiac Fibroblasts Induced by Chymase
Xiaoyan ZHAO ; Lianyou ZHAO ; Qiangsun ZHENG ; Yongfei AI
Chinese Journal of Hypertension 2006;0(08):-
Background Cardiac mast cell-derived chymase is involved in myocardial fibrosis,but the underlying mechanisms remain unclear. Objective To investigate the effect of chymase on the collagen synthesis and its relationship with transforming growth factor-?1 (TGF-?1)/Smad pathway in rat cardiac fibroblasts (CFs). Methods CFs,from neonatal SD rats,were isolated by trypsinization. The collagen synthesis of CFs was determined by 3H-proline incorporation. The protein expressions of TGF-?1,phosphorylated Smad2/3 (P-Smad2/3) and total Smad2/3 were determined by immunoblotting in CFs. Results Chymase (15,30 and 60 ?g/L) increased the 3H-proline incorporation in a concentration-dependent manner. 30 ?g/L chymase stimulation increased the protein expressions of TGF-?1 and P-Smad2/3 in a time-dependently,while little effect on Smad2/3 protein expression was found. The stimulatory effect of chymase on 3H-proline incorporation elicited by 30 ?g/L chymase was blocked in the presence of TGF-?1 antibody or staurosporine,a P-Smad2/3 inhibitor. Conclusion Chymase promotes collagen synthesis of rat CFs,TGF-?1/Smad might be involved into the signal pathway.
6.Inhibitory effect of cyclosporin A on growth and collagen synthesis of rat cardiac fibroblasts induced by arginine vasopressin
Fujun SHANG ; Lianyou ZHAO ; Qiangsun ZHENG ; Jiepin WANG
Acta Pharmaceutica Sinica 2006;41(11):1044-1049
Aim To investigate the effects of cyclosporin A (CsA) on growth and collagen synthesis of cardiac fibroblasts (CFs) induced by arginine vasopressin (AVP). Methods CFs of neonatal Sprague-Dawley rats were isolated by trypsinization and cultured; growth-arrested CFs were stimulated with 1×10-7 mol·L-1 AVP in the presence or absence of CsA (0.05, 0.5 and 5 μmol·L-1). MTT and flow cytometry techniques were adopted to measure cell number and analyze cell cycle respectively. Collagen synthesis was determined by measurement of hydroxyproline content in culture supernatant with colorimetry. Calcineurin activity was estimated by chemiluminescence. Trypan blue staining to test the viability of CFs. Results 0.05, 0.5 and 5 μmol·L-1 CsA inhibited the increase of CFs number induced by 1×10-7 mol·L-1 AVP in a dose-dependent manner, with the inhibitory rates by 12%, 24% and 29%, respectively (P<0.05). Furthermore, cell cycle analysis showed 0.5 μmol·L-1 CsA decreased the S stage percentage and proliferation index of CFs stimulated by AVP (P<0.05). In culture medium, the hydroxyproline content induced by AVP decreased by 0.5 and 5 μmol·L-1 CsA (P<0.05), with the inhibitory rates of 29% and 33%, respectively. CsA completely inhibited the increment of calcineurin activity induced by AVP (P<0.01), but CsA itself had no effect on the baseline of calcineurin activity and CFs viability. Conclusion CsA inhibits proliferation and collagen synthesis of CFs by virtue of blocking calcineurin signaling pathway and might provide a novel target for prevention and treatment to cardiac fibrosis.
7.The GRACE risk score predicts no-reflow and MACE in patients with STEMI undergoing PCI
Zhaofei WAN ; Sumei ZHANG ; Yan FAN ; Xiaojun LIU ; Xinhong WANG ; Jiahong XUE ; Qiangsun ZHENG
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(2):251-256
【Objective】 Coronary no-reflow during percutaneous conranary intervention (PCI) often results in the failure of ischemic myocardial reperfusion and major adverse cardiovascular events (MACE). The present study sought to evaluate whether the GRACE risk score can predict coronary no-reflow in STEMI patients undergoing PCI. 【Methods】 We consecutively recruited 1 118 patients with STEMI who were admitted to Gansu Provincial People’s Hospital and The First Affiliated Hospital of Xi’an Jiaotong University from January 2009 to December 2011. Main demographic data, cardiovascular risk factors, blood lipid and other biochemical indicators were recorded. Coronary angiography was performed by a radial artery approach using the standard Judkins technique. Coronary no-reflow was evaluated by at least two independent experienced cardiologists. The GRACE risk score was calculated with a computer program. All the cases were followed up by medical records, face-to-face interviews or telephone calls. Finally, we analyzed the predictive value of the GRACE risk score for coronary non-reflow and MACE in STEMI patients undergoing PCI. 【Results】 During a median period of 36 months, 58 of the 1 118 patients (5.2%) were lost to follow-up. Of the remaining 1 060 patients, 118 (11.1%) had no-reflow and 147 (13.9%) had MACE. The GRACE score was higher in patients with no-reflow than those without no-reflow. Multivariate logistic regression established that the GRACE score was an independent predictor for coronary no-reflow (OR=1.034; P=0.002). And multivariate Cox analysis showed the GRACE score was an independent predictor of MACE. The area under the ROC curve for coronary no-reflow and MACE was 0.719 and 0.697, respectively. Kaplan-Meier analysis showed that the probability of rehospitalization for heart failure, reinfarction, all-cause death and cumulative cardiovascular events increased with the increase of the GRACE risk score. 【Conclusion】 The GRACE risk score is a readily available predictive scoring system for coronary no-reflow and MACE in STEMI patients.