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This study was aimed to explore the combined effects of Exendin-4 with dipeptidyl peptidase-IV [DPP-4] silencing on vascular endothelial growth factor [VEGF]-induced cell proliferation and angiogenesis in Human Coronary Artery Endothelial Cells [HCAECs], as well as the underlying molecular mechanisms which were involved in this process. HCAECs were treated by exendin-4, small interfering RNA [siRNA] targeting DPP-4 [DPP-4-siRNA] or exendin-4 plus DPP-4-siRNA, respectively. Cell migration, proliferation and angiogenesis in vitro were assessed by scratch-wound assay, MTT, tran swell assay, and matrigel tube formation, respectively. Cell apoptosis was investigated by TUNEL assay. Expression of apoptosis and PI3K/Akt related proteins were assessed by Western blotting. Incubation of HCAECs with exendin-4 and silencing of DPP-4 both caused an increase in cell proliferation, migration and tube formation, while a significant decrease in apoptosis [all p<0.05]. Furthermore, the combination of the exendin-4 and silencing of DPP-4 had additional effects on HCAECs. Protein levels of p-Akt and p-PI3K were markedly increased by exendin-4 incubation, silencing of DPP-4 in HCAECs. These results suggest that combination of exendin-4 and silencing of DPP-4 had additional promoted effects on angiogenesis of HCAECs via activation of PI3K/Akt pathway. Our study indicated an alternative therapeutic strategy for atherosclerotic neovascularization
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OBJECTIVE:To investigate the clinical efficacy and safety of alprostadil in the treatment of heart failure in pa-tients with normal left ventricular ejection fraction (LVEF). METHODS:120 patients diagnosed as heart farlture with normal LVEF were divided into observation group and control group by radom number table method,with 60 cases in each group. Control group was given symptomatic treatment;observation group was additionally treated with Alprostadil dried emulsion for injection 10μg,bid,on the basis of control group. Both groups received treatment for 5 d. The cardiac function indexes,serum inflammatory factors and oxidative stress indexes were observed in 2 groups before and after treatment,and the occurrence of ADR was com-pared between 2 groups. RESULTS:Before treatment,there was no statistical significance in cardiac function indexes,serum in-flammatory factors and oxidative stress indexes between 2 groups (P>0.05). After treatment,above indexes of 2 groups were all improved significantly,and the observation group was significantly better than the control group,with statistical significance(P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:Alprostadil can improve cardiac function of patients with heart failure of normal LVEF,improve serum inflammatory factors and oxidative stress level with good safety.
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Objective: To observe influence of anxiety or depression on prethrombotic state in patients with essential hypertension (EH). Methods: A total of 112 EH patients were equally divided into EH + A/D group and pure EH group. Levels of prethrombotic state indicators, including serum CD62P, von Willebrand factor (vWF), tissue type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI)-1 and endothelin (ET)-1 were measured in two groups. Results: Compared with pure EH group, there were significant increase in levels of CD62P [(4.52±2.01) % vs. (8.38±1.96) %], vWF [(155.28±23.11) % vs. (185.23±22.21) %], PAI-1 [(54.35±13.21) ng/L vs. (79.88±14.53) ng/L] and ET-1 [(121.56±33.32) ng/L vs. (152.78±30.23) ng/L], P<0.05 all; and significant decrease in t-PA level [(19.37±11.46) ng/L vs. (9.56±8.32) ng/L, P<0.05] in EH + A/D group. Conclusion: Anxiety or depression can aggravate prethrombotic state of patients with essential hypertension through activation of platelets, influencing vascular endothelial function and fibrinolytic system imbalance.
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Objective To explore the effect and mechanism of atorvastatin on pulmonary hyper-tension in chronic pulmonary heart disease.Methods Sixty eight patients with chronic pulmonary heart disease were randomly divided into treatment group (n=35) and observation group ( n=33 ).Thirty healthy people were picked up from people taking physical examination at the same stage as control group.Patients in both treatment and observation groups were given routine treatment and the observation group were given atorvastatin (20 mg/d) supplement.Changes in pulmonary function,ultrasound cardiogram,plasma high-sensitive C-reactive protein (hs-CRP) and interleukin (IL-8) were observed before and after 6 months of treatment.Results The levels of hs-CRP,IL-8 and pulmonary arterial pressure in treatment and observation groups are higher than that in normal group before treatment (t=2.87,2.79,3.01,3.28,3.31,3.15,respectively,and P =0.005,0.007,0.004,0.001,0.001,0.002,respectively).The pulmonary arterial pressure,hs-CRP,IL-8 in observation group after treated for 6 months were significantly lower than those before treatment and in treatment group (t=2.17,2.59,2.63,1.91,1.86,1.74,respectively,and P =0.039,0.008,0.007,0.031,0.037,0.042,respectively).The pulmonary function indexes including FEV1 and FEV1/FVC in observation group were much better than those in treatment group after 6 months treatment (t=1.84,2.13,respectively,and =0.037,0.024,respectively).There were no significant differences on these indicators in treatment group after 6 months treatment when compared with before treatment ( P ＞ 0.05 ).Conclusion Atorvastatin can effectively improve the life quality and pulmonary function,decrease pulmonary arterial pressure of patients with chronic pulmonary heart disease.These effects may be related to the inhibition of inflammation in pulmonary vessels.
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Objective To explore the effect of endothelial progenitor cells (EPCs) on the development of collateral formation in stable angina patients with serious coronary artery disease.Methods The subjects were patients ( n =92) who underwent coronary angiography (CAG) and had chronic total occlusion (CTO) in one major coronary artery.They were divided into two groups,patients without collaterals (coil-,n =50) and patients with collaterals (coll +,n =42).EPCs were isolated from peripheral blood samples and cultured.The numbers of colony-forming units (CFUs) and the vasculargenesis capacity in vitro was assayed respectively.The plasma level of SDF-1α was determined by enzyme linked immunosorbent assay.Results The number of colony-forming units ( CFUs ) [ ( 22.10 ± 4.69 ) CFUs/106 EPCs vs ( 16.90 ± 3.66) CFUs/106 EPCs ],vasculogenesis capacity in vitro (25.3 ± 3.2 vs 17.4 ± 2.6) and plasma level of SDF-1 α[ (243.7 ± 19.2 ) ng/ml vs ( 203.1 ± 17.8) ng/ml,P ＜ 0.01 ] in coll + group were higher than that of coll group.It had a positive correlation between the level of collateral circulation and the numbers of CFUs,vascular genesis activity of circulating EPCs and plasma level of SDF-1αt( r =0.74,0.69,0.82,0.81,0.64,P ＜ 0.01 ).Conclusions The number of CFUs and vasculargenesis activity of EPC in coll + group with serious coronary artery disease is significantly higher than that in coll- group.These changes may be related to the increase of plasma SDF-1 α.The method improving the numbers and function of EPCs,increasing the activity of SDF-1 α may benefit the patients with coronary artery disease.
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Objective To investigate the changing of endothelial progenitor cells and nitric oxide in patients with pulmonary arterial hypertension secondary to chronic obstructive pulmonary disease.Method Mononuclear cells from 20 healthy persons (the control group, n = 20) , COPD patients without PAH (COPD non-PAH group, n =30) and patients with PAH secondary to COPD (COPD and PAH group, n=30) were investigated. Total mononuclear cells were isolated from peripheral blood by Ficoll density gradient centrifugation. EPC number and migration were assayed by colony forming unit-EPCs (CFU-EPCs) assay and modified Boyden chamber assay , respectively. EPC adhesion assay was performed by replanting those on fibronectin-coated dishes , then adherent cells were counted. The concentration of NO was measured with method of nitrate reductase.Result The numbers of CFU and migration, adhesion activity of circulating EPCs in COPD[ (21.9±3. 9)CFU-EPC] and PAH group[ (14. 2 ±3. 5)CFU-EPC] were significantly lower than that in non-COPD group and COPD non-PAH group [ ( 24.9 ±4.1) CFU-EPC ]. It was also observed that a strong negative correlation between the levels of PAH and the numbers of CFU and adhesion, migration activity of circulating EPCs. The NO level in the PAH group [ (43. 6 ±4. 8)ng/ml] was significantly lower than that in control group [ ( 67. 17±4.9 ) ng/ml ] ( P < 0.01). The NO level was positively correlated with number and migration ability of EPCs( r =0. 77,0.71, P <0.01) , but not correlated with adhesion ability.Conclusion The number of CFU and migratory, adhesive activity of EPC in patients withPAH secondary to COPD was significantly decreased. These changes may be associated with low level of plasma NO.
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<p><b>OBJECTIVE</b>To determine the feasibility and efficiency of terminating atrial flutter (AFL) and atrial fibrillation (AF) using synchronous low-energy shocks delivered through a novel transesophageal electric balloon electrode system.</p><p><b>METHODS</b>By using a novel electric balloon electrode system, we attempted 91 transesophageal cardioversions in 52 patients, to treat 53 episodes of AFL and 38 episodes of AF.</p><p><b>RESULTS</b>Of the 40 patients of AFL that failed to respond to drug therapy, 37 (92.5%) were successfully countershocked to sinus rhythm by transesophageal cardioversion, with a mean energy of (22.70 +/- 4.50) J (20 - 30 J). Of the 19 patients in AF, transesophageal cardioversion was successful in 16 (84.2%) cases, requiring a mean delivered energy of (17.38 +/- 8.58) J (3 - 30 J). There were no complications such as heart block or ventricular fibrillation, and no evidence of esophageal injury.</p><p><b>CONCLUSIONS</b>Transesophageal cardioversion using an electric balloon electrode system is an effective and feasible method for the treatment of AFL and AF. It requires low energy and no anesthesia, leads to less trauma, and shows a high cardioversion success rate that may prove valuable in the management of tachyarrhythmias.</p>