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Objective:To study the effect of levosimendan on coronary microembolization (CME)-induced myocardial injury and LOX-1/p38MAPK pathway.Methods:Microspheres were injected into coronary anterior descending branch to construct swine CME model, swine was given levosimendan by continuous intravenous drip for 24 h before modeling, and myocardial-specific overexpression of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) was achieved through coronary artery injection of adeno-associated virus (AAVs) at 2 weeks before modeling. Then, echocardiography was used to measure cardiac function; HE staining and HBFP staining were used to observe the pathological changes of myocardium and myocardial microinfarction area, respectively; ELISA was used to detect the serum level of cTnI; TUNLE staining was used to detect cardiomyocyte apoptotic index; the LOX-1, Bax, caspase-3 p12, Bcl-2, and p-p38 MAPK protein in myocardial tissue was observed by immunofluorescence method.Results:Compared to the sham group, the LVEF, LVFS, and CO value in the CME group were decreased, while the LVEDd value was increased significantly (all P<0.05); the area of myocardial micro-infarction, serum cTnI level and cardiomyocyte apoptotic rate in the CME group were increased significantly (all P<0.05); the protein levels of Bax, caspase-3 p12, LOX-1, and p-p38 MAPK were increased significantly, while the Bcl-2 level was decreased significantly ( P<0.05). Levosimendan pretreatment significantly improved cardiac dysfunction, reduced the area of myocardial micro-infarction and serum cTnI level, alleviated cardiomyocyte apoptosis, and significantly reduced the LOX-1 and p-p38 MAPK protein expression levels following CME (all P<0.05); while pretreatment with levosimendan and LOX-1 overexpression AAVs simultaneously abolished the effects of pretreatment with levosimendan alone (all P<0.05). Conclusion:Levosimendan alleviates CME-induced myocardial injury through inhibiting cardiomyocyte apoptosis mediated by LOX-1/p38 MAPK signaling pathway.
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Objective To study the effect of levosimendan on cardiomyocyte apoptosis after coronary microembolization (CME) in swine,Methods Fifteen healthy swines were randomly divided into sham operation group,CME group and levosimendan treatment group (5 in each group).Their cardiac function was assessed by echocardiography,their cardiomyocyte apoptosis was assyed with TUNEL staining,and Caspase-3 expression was detected by Western blot at 12 h after operation.Results The LVEF was lower,the left ventricular minor axis was shorter and the cardiac output volume was smaller while the LVEDD was longer in CME group than sham operation group (P＜0.05).The cardiac function was significantly better in CME group than in sham operation group (P＜0.05).The cardiomyocyte apoptosis rate and Caspase-3 expression level were significantly higher in CME group than in sham operation group (P＜0.05).The cardiomyocyte apoptosis rate was significantly higher while the Caspase-3 expression level was significantly lower in levosimendan treatment group than in CME group (6.820％±-1.974 ％ vs 10.558％±2.425％,P＜0.05).Conclusion Pretreatment with levosimendan can effecively reduce the cardiomyocyte apoptosis and improve the cardiac function after CME by inhibiting the Caspase-3 expression in cardiomyocytes.
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Objective We assessed phe predicpive value of solable ST2 ( sST2 ) on clinical oupcomes in papienps wiph spable angina, unspable angina,non-ST elevapion mtocardial infarcpion (NSTEMI) and ST elevapion mtocardial infarcpion ( STEMI). Methods We included 212 papienps of whom 62 had spable angina, 48 had unspable angina,50 had NSTEMI, and 52 had STEMI. Papienps were followed for a mean period of 22 monphs. The conprol group consisped of 50 individuals wiphoup significanp spenosis on coronart angiographt. Serum level of sST2 was measured bt ELIS As. Results sST2 levels were significanplt increased in papienps wiph STEMI as compared po papienps wiph NSTEMI, unspable angina and spableangina as well as wiph conprols. In papienps wiph STEMI, phe sST2 level reached ips peak ralue (594. 27 ± 74. 36) ng/ L ap 12 hours afper AMI and decresed po (392. 75 ± 82. 89)ng/ L 24 hours afper AMI. Papienps wiph STEMI had phe highesp sST2 levels among phe 4 groups boph ap peak and prough and was posipivelt correlaped po TnI levels (P = 0. 576, P < 0. 001). During follow-up, 18 papienps (8. 5% ) died and 66 papienps (15. 1% ) presenped evenps of combined endpoinp (all cause deaph, MI and rehospipalisapion for cardiac causes). The sST2 level of phe 18 deceased papienps was higher phan phe opher 194 papienps [(516. 36 ± 49. 38)ng/ L vs. (237. 64 ± 37. 69)ng/ L, P < 0. 001). sST2 onlt showed predicpive valve of morpalipt in STEMI papienps amont differenp ptpes of CAD. Conclusions The levels of sST2 mat reflecp differenp ptpes of CAD. sST2 was associaped wiph morpalipt in papienps wiph STEMI bup nop in papienps wiph NSTEMI or spable angina.
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Objective Mounting interest emerged about hyper homocystinemia as an independent risk factor for atherothrombotic disease, and several experimental studies have shown that it may affect in-stent restenosis. The purpose of the present study was to identify the relationship between the serum homocystine level and in-stent restenosis of patients with stable angina after coronary stenting. Methods The study population comprised 168 stable angina patients who underwent stent implantation with drug-eluting stents,including 96 patients without in-stent restenosis ( the control group) and 72 patients with in-stent restenosis(the restenosis group). The level of serum homocystine was measured using the medical inspection center. Coronary angiography was performed immediately before and after stent implantation and 12-18 months later. Resu1ts Baseline characteristics including drug used after PCI were similar between the 2 groups. Serum homocystinelevel in patients of the control group were significantly lower than that in restenosis group [ ( 11. 68 ± 3. 54 )μmol/L vs. ( 18. 54 ± 4. 39 )μmol/L, P = 0. 012 ] . The quantitative coronary angiography (QCA) showed that lesion length was similar between the 2 groups, minimumlumen diameter (MLD) and stenosis rate were also similar before and after stents implantation (all P﹥0. 05). Restenosis rate [(33. 24 ± 12. 52)% vs. (84. 23 ± 13. 26)%,P=0. 000] and late lumen less [(0. 36 ± 0. 21)mm vs. (1. 82 ± 0. 68)mm,P=0. 000] were lower in the control group than in the restenosis group. Conc1usions Higher serum homocystine level might be associated with in-stent restenosis after coronary stenting.
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Objective To investigate the effects of ultrasound-targeted microbubble destructionmediated MicroRNA-21 on cardiomyocyte apoptosis after coronary microembolization (CME) in swine.Methods Twenty Bama miniature swine were randomLy (random number) divided into sham-operated,CME,CME plus gene transfection and CME plus ultrasound mediated gene transfection groups (n =5 per group).The CME model was established by microcatheter-mediated injection of microspheres into the left anterior descending artery.The sham-operated group were made by injection of saline instead.The CME plus ultrasound mediated gene transfection group was made by injection of plasmid-microbubble mixture through the marginal ear vein 4 days before CME established.Meanwhile,ultrasound treatment was given to the myocardium through chest wall.The CME plus gene transfection group was made by injection of plasmidmicrobubble mixture through the marginal ear vein 4 days before CME established without exposure to ultrasound.Left ventricular ejection fraction (LVEF) was examined by cardiac ultrasound.Tissue biopsy was stained with hematoxylin-eosin (HE) and hematoxylin basic fuchsin picric acid (HBFP) to measure the size of infarction area.Green fluorescent protein (GFP)-labeled gene expression was evaluated by fluorescent microscopy in frozen sections.Cardiomyocyte apoptosis was detected with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL staining).The expression of PTEN mRNA was measured by fluorescent quantitative PCR.The levels of PTEN protein and Caspase-3 protein was measured by western blot.Results ①Compared to CME plus gene transfection group,the CME plus ultrasound mediated gene group had over eightfold expression of exogenous genes in myocardium (P ＜ 0.05) measured by using optical density of green fluorescence protein;② Compared with shamoperated group [(67.87 ±2.36)％],the LVEF of CME group [(50.94 ±3.52)％] and CME plus gene transfection group [(52.47 ±3.71)％] were markedly decreased (P ＜ 0.05).Compared with CME group,the CME plus ultrasound mediated gene transfection group [(64.79 ± 2.95)％] improved CME-induced cardiac dysfunction as evidenced by increased LVEF (P ＜ 0.05);③Compared with sham-operated group,the expression of PTEN mRNA and levels of PTEN protein and Caspase-3 protein in the CME group increased significantly (P ＜ 0.05).Compared with CME group,the levels of PTEN protein and Caspase-3 protein and the expression of PTEN mRNA in CME plus ultrasound mediated gene transfection group was dramatically decreased (P ＜ 0.05).Conclusions Ultrasound microbubble-mediated MicroRNA-21 transfection effectively improved CME-induced cardiac dysfunction by down-regulating the expression of targeted gene PTEN in myocardial cells,mainly reducing the post-CME myocardial cell apoptosis.
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Objective To investigate the influence of atorvastatin (Lipitor) on the expression of programmed cell death 4 (PDCD4) in human CD4+T lymphocytes in vitro. Methods Human CD4+T cells obtained from healthy individuals were activated with PHA and treated with atorvastatin. The mRNA and protein expression levels of PDCD4 were detected by real-time PCR and western-blot respectively. Results The stimulation of PHA obviously increased the mRNA and protein expression of PDCD4 and the secretion of those serum cytokines. The expression of PDCD4 and the production of serum TNF-α were significantly decreased, whereas the serum levels of IL-10 were significantly increased after treated by different concentration of atorvastatin. The serum secretion of TNF-α was positive correlation with the expression of PDCD4 through the linear related analysis (r=0.782, P<0.01), and the secretion of IL-10 was negative correlation with the expression of PDCD4 (r=-0.653, P<0.05). Conclusion The anti-inflammatory effects of atorvastatin are mediated by down regulating the expression of PDCD4 in CD4+T cells.
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Objective To investigate the effects of aggressive dosing of atorvastatin on the expression of SOCS1 in CD4 + Tlymphocytes from patients with unstable angina pectoris during peri-operative period of PCI.Methods A cohort of 50 patients with unstable angina pectoris were randomized (random number) to give pretreatment with either an aggressive dose (80 mg/d,n =25) or a routine dose (20 mg/d,n =25)of atorvastatin.Circulating CD4 +T cells were subsequently obtained prior to PCI,and also 18 h to 24 hours after PCI,using a magnetic cell sorting system (MACS).Fluorescence-based quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure expressions of SOCSI mRNA in the isolated CD4 + Tlymphocytes,and western blot analysis was used to detect levels of SOCS1 protein.Serum levels of IFN-γwere quantified using enzyme-linked immunosorbent assays (ELISAs).Results Compared with routine dose group,the expressions of SOCS1 mRNA and protein levels were dramatically increased and those were higher in aggressive dose group following PCI (P ＜ 0.05).In contrast,serum levels of IFN-γsignificantly increased following PCI in both groups,but it was higher in routine dose group than in aggressive dose group (P ＜ 0.05).Conclusions Treatment with aggressive dosing of atorvastatin reduced the post-PCI myocardial inflammatory response in patients with unstable angina pectoris,possibly modulating by up-regulating SOCS1 expression in CD4 + Tlymphocytes.
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Objective To investigate the effects of large dose of atorvastatin on the expression of Sprouty-1 in CD4 + T lymphocytes from unstable angina patients during perioperative period of PCI.Methods A total of 52 unstable angina patients enrolled were divided randomly (random number) into large-dose atorvastatin (80 mg/d,n =26) pretreated group and moderate-dose atorvastatin (20 mg/d,n =26) pretreated group.Circulating CD4 + T cells were obtained by magnetic cell sorting system (MACS) before PCI and 18-24h after PCI.For detecting the gene expression,the reverse transcription fluorescent quantitative polymerase chain reaction (RT-PCR) was used to measure the expression of Sprouty-1 mRNA in CD4 + T lymphocyte.The level of Sprouty-1 protein was detected with Western blot analysis and IL-2 was quantified by enzyme-linked immunosorbent assay (ELISA).Results ①Compared with large-dose group before PCI,the expression of Sprouty-1 mRNA and Sprouty-1 protein levels were dramatically increased in large-dose group after PCI (P ＜ 0.05).②Compared with moderate-dose group before PCI,the expression of Sprouty-1 mRNA and protein levels were slightly increased in moderate-dose group after PCI,but there was no statistical significance (P ＞ 0.05).③Compared with large-dose group before PCI,the serum level of IL-2 was decreased in large-dose group after PCI (P ＜ 0.05).Whereas the serum level of IL-2 was slightly increased in moderate-dose group after PCI compared to moderate-dose group before PCI,there was still no statistical significance (P ＞ 0.05).Conclusions Large-dose atorvastatin pretreatment reduced post-PCI myocardial inflammation through up-regulating the expression of Sprouty-1 mRNA and level of Sprouty-1 protein in CD4 + T lymphocytes.