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Objective To investigate the long-term toxicity of anti-inflammatory and anticoagulant tick anticoagulant peptide (TAP)-staphylococcal superantigen like protein-5 (SSL5) fusion protein in normal rats.MethodsSD rats were intraperitoneally injected with TAP-SSL5 (1mg/kg, every other day) for eight weeks and followed up for one week.The general behavior, weight, blood routine test, blood biochemistry and organ indexe were measured.ResultsOur results showed that there were no significantly difference between the TAP-SSL5 treated rats and the control on general behavior, weight, blood routine test, blood biochemistry, organ indexe and pathology.ConclusionThe fusion protein TAP-SSL5 with little long-term toxicity for rats is proved to be a safe drug.
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Objective: To investigate the effect of fusion protein tick anticoagulant peptide (TAP)-staphylococcus aureus superantigen-like protein 5 (SSL5) on the formation of atherosclerotic plaque in ApoE knockout (ApoE-/-) mice.Methods: Totally 21 male 12-week-old ApoE-/-mice were randomly divided into three groups: TAP-SSL5 (3 mg·kg-1·d-1) group, SSL5 (2 mg·kg-1·d-1) group and the blank control group (pH 7.4 phosphate buffer), ip, qd, for 12 weeks.The changes of body mass were observed.The mice were fed with high cholesterol diet for 12 weeks, and then the levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) in plasma were detected.The aorta of mice was subjected to paraffin section and routine HE staining.The formation of atherosclerotic plaque in the aortic root was analyzed.The distribution of atherosclerotic plaques was observed by oil red O staining of the aorta.Results: Compared with that of the blank control group, the increasement of body weight of TAP-SSL5 group and the level of TC significantly decreased (P <0.001), while TG, HDL-C and LDL-C did not change significantly.The HE staining results showed that the plaque area of root slice in the aorta in TAP-SSL5 group was significantly lower than that in the blank control group (P<0.05).The red O staining of aorta showed that the formation of atherosclerotic plaque in TAP-SSL5 group was significantly smaller than that in the blank control group.Conclusion: TAP-SSL5 can significantly inhibit the formation of atherosclerotic plaques in the arteries of ApoE-/-mice.
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AIM:Early calcification of atherosclerotic plaques are colocalized with macrophage and high mobility group box 1 (HMGB1), a cytokine associated with biomineralizing process under physiological and pathological conditions .Our study aims to evaluate whether HMGB1 induces ectopic mineralization via promoting the secretion of matrix vesicles ( MVs) from macrophages .METHODS:HMGB1 was added to the medium of macrophages , the secretion of MVs in the supernatant was tested by flow cytometry analysis .The mineral deposition in calcifying medium was detected by Alizarin Red staining and von Kossa staining .Transmission electron microscopy showed the formation of hydroxyapatite crystals in MVs .Then we subcutaneous injection into mice with MVs to induce regional minera-lization.RESULTS:HMGB1 significantly promoted secretion of MVs from macrophages as raveled by flow cytometry analysis .TNAP activity, considered as a marker of MVs maturation , was higher in HMGB1-induced MVs compared to the control-MVs.HMGB1-MVs also led to mineral deposition in an in vitro MVs-collagen mineralization model .Subcutaneous injection into mice with MVs derived from HMGB1-treated cells showed a greater potential to initiate regional mineralization .Mechanistic experiments revealed that HMGB 1 activated neutral sphingomyelinase 2 ( nSMase2 ) that involved the receptor for advanced glycation end products ( RAGE ) and p38 MAPK (upstream of nSMase2).Inhibition of nSMase2 with GW4869 or p38 MAPK with SB-239063 prevented MVs secretion and min-eral deposition .CONCLUSIONS: HMGB1 induces MVs secretion from macrophages at least in part , via the RAGE/p38 MAPK/nSMase2 signaling pathway .Our findings thus reveal a novel mechanism by which HMGB 1 may participated in the early calcification of atherosclerotic plaques .
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AIM: To study the effect of tick anticoagulant peptide-staphylococcal superantigen like protein 5 (TAP-SSL5), an anti-inflammatory and anticoagulant fusion protein , on the binding of activated platelets to human lym-phocytes.METHODS:Human periphery lymphocytes were isolated by magnetic activated cell sorting (MACS).The toxic-ity of TAP-SSL5 on the viability of Jurkat cell was assessed by CCK-8 assay.Flow cytometry was applied to detect the ex-pression of CD162 (PSGL-1) on the Jurkat cells (human peripheral blood leukemia T lymphocyte cell line ) and the inhibi-tory effect of TAP-SSL5 on the binding of mouse anti-human CD162 monoclonal antibody (KPL-1) to Jurkat cells.Platelets were activated by ADP at concentration of 20μmol/L, the binding rates of activated platelets to Jurkat cells or human lym-phocytes were assayed by flow cytometry .RESULTS:The concentration of TAP-SSL5 below 30 mg/L didn’ t affect the vi-ability of Jurkat cells .TAP-SSL5 at 10 mg/L competitively inhibited KPL-1 binding to Jurkat cells .The binding rates of activated platelets to Jurkat cells or lymphocytes were (11.86 ±4.49)% and (8.32 ±1.00)%, respectively, which de-creased to (6.73 ±2.71)%and (5.51 ±0.70)%after the Jurkat cells and lymphocytes were pre-incubated with 10 mg/L TAP-SSL5 (P <0.05).CONCLUSION:TAP-SSL5 binds to PSGL-1 expressed on lymphocyte surface and directly in-hibits the binding of activated platelets to human lymphocytes , which may be one of the anti-inflammatory mechanisms of TAP-SSL5.
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Objective To systematically evaluate the clinical outcomes of patients with multivessel diseases treated by fractional flow reserve (FFR) guided percutaneous coronary intervention (PCI) or other forms of treatment .Methods Some keywords inclu-ding FFR or fractional flow reserve ,percutaneous coronary intervention or PCI ,multivessel coronary artery disease were used to search randomized control trails(RCT) ,which compared outcomes of patients with multivessel disease treated by FFR guided PCI with other forms of treatment ,in Chinese and English database including CNKI ,VIP ,Wanfang ,Pubmed ,EMBASE and the web of science .The quality of included studies was evaluated by Jadad quality score and all the data was analyzed by stata 10 .0 .Results A total of 7 english literatures accumulating 2024 cases in experimental group and 7 284 cases in control group were included in this study .Compared with other forms of treatment ,patients with multivessel diseases treated by FFR-guided PCI had significantly low-er risk of myocardial infarction (RR=0 .72 ,P=0 .008) .Although the risk of death and major adverse cardiovascular events were al-so be reduced ,there were no statistically significant difference .Conclusion FFR-guided PCI is an effective treatment for multivessel disease ,but it is still needs further verification for the application in Chinese population .
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@#Objective To observe the curative effects of long term statins treatment on blood lipid and left ventriclar function of myocardial infarction patients. Methods 70 patients with myocardial infarction were randomly divided into two groups: Statins treatment group (n=37) and control group (n=33). The level of blood lipid, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF) were mearsured before and 2 years after the treatment. Results The long term applies of statins can bring statistically different (P<0.05) of TC and LDL-C to myocardial infarction patients. LVESD and LVEF were statistically different (P<0.05) before and after statins were used. Conclusion The long term applies of statins can improve the lipidic metabolism and left ventricular function after myocardial infarction.
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Objective To investigate the effects of liver X receptor agonist on the expressions of C-reactive protein and CD40 ligand and smooth muscle cell ?-actin in the aorta of ApoE gene knockout mice with earlier atherosclerosis. Methods Male ApoE gene knockout mice (8-week old) were divided randomly into control group and T0901317 treatment group (n=6 in each group). The mice in T0901317 group were administered intraperitoneally with T0901317 at the dose of 20 mg?kg-1?d-1 for 4 weeks. Mice in the control group were only given equivalent amount of dimethyl sulfoxide (DMSO). The expressions of C-reactive protein and CD40 ligand and smooth muscle cell ?-actin were detected by immunological histochemical method. Results The expressions of C-reactive protein and CD40 ligand in the atherosclerotic plaque in the aortic wall were significantly lower in T0901317 group as compared with those in the DMSO control group (P0.05). Conclusion Liver X receptor agonist may reduce the formation of atherosclerotic lesions by inhibiting the inflammation and the expressions of C-reactive protein and CD40 ligand in the aorta of ApoE gene knockout mice.
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Objective To investigate the effects of celastrol on the expressions of macrophage migration inhibitory factor(MIF)and matrix metalloproteinase-9(MMP-9)in the aorta of apoE gene knockout mice with earlier atherosclerosis.Methods Eight-week-old ApoE gene knockout male mice were divided randomly into control group and celastrol treatment group(n=6 in each group).The mice in celastrol group were given.celastrol(2 mg?kg-1?d-1)by intraperitoneal injection for 4 weeks;and the mice in control group were only given equivalent amount of dimethyl sulfoxide(DMSO).HE staining of root aorta were used to observe the histomorphological changes and measure the size of plaque in ApoE-/-mice.The expressions of MIF and MMP-9 were detected by immunological histochemical method.Results The area of lipid plaque in the mice treated with celastrol was significantly smaller than that of the control(P
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Objective To evaluate the immediate and short term therapeutic efficacy of percutaneous transluminal septal myocardial ablation (PTSMA) in patients with hypertrophic obstructive cardiomyopathy (HOCM) and to investigate the prevention of the related complications. Methods PTSMA was conducted in 3 patients with HOCM refractory to medication. The immediate effect was evaluated by pressure monitor, but the follow up effect by observation of the clinical symptoms and ultrasonic cardiogram. Results The left ventricular outflow tract gradients triggered by ventricular premature beats decreased from 143 mmHg (ranging from 70 to 180 mmHg) to 53 mmHg (ranging from 30 to 80 mmHg). Complete atrioventricular block (Ⅲ?AVB) with atrioventricular node rhythm was found in 1 case, and complete right branch bundle block (CRBBB) in another one. Follow up of the 3 cases at 6 months after operation revealed remarkable improvement of the patients' cardiac function (NYHA), disappearance of angina pectoris, and obvious attenuation of ventricular septal hypertrophy and SAM (systolic anterior motion of mitral) phenomenon. Conclusion PTSMA is an effective method with satisfactory short term effect for the patients with HOCM refractory to medication.
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Objective To evaluate the therapeutic efficacy and safety of transcatheter closure of atrial septal defect (ASD) and patent ductus arteriosus (PDA) using Amplatzer occluder. Methods Routine cardiac catheterization and angiography were performed in 50 patients (23 male, 27 female, age ranging from 3 to 64 years old), including 19 cases of ASD and 31 cases of PDA under local or general anesthesia. After balloon sizing of the ASD, the optimal Amplazter septal occluder (ASO) was transmitted into the left atrial, and the left and right disks were released in turn. The Amplatzer occluder was completely released after transthoracic echocardiography confirmed that there was no residual shunts or new onset mitral valve regurgitation. The Amplatzer duct occluder (ADO) size was selected according to the narrowest point of PDA measured by angiography, and the occluder was released after the repeated angiography showed no residual shunts. Results ① The mean diameter of the ASD measured by balloon was 13-31 (23?6) mm and the diameter of ASO was (17-40) mm. The immediate closure rate was 100%. ② Angiography confirmed that closure of the ductus using ADO was achieved in 30 patients, and closure of the large size (12 mm) was achieved in 1 case of PDA patient using ASO (17 mm). No complications were encountered. Conclusion Transcatheter closure of ASD and PDA using Amplatzer device, with the advantages of simple operation, confirmative occlusion efficacy, minimal invasiveness, wide indications, and less complications, has a bright future of clinical application.
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AIM: To study the effects of oxidized high-density lipoprotein (oxHDL) on the expression of monocyte chemoattractant protein-1(MCP-1) and intercellular adhesion molecule-1(ICAM-1) and intracellular free calcium concentration （［Ca2＋］i） level in cultured human umbilical venous endothelial cells(HUVECs). METHODS: The MCP-1 protein content in the medium of conditioned HUVEC was measured by ELISA, and the ICAM-1 on HUVECs was detected by indirect immunofluorescence, and ［Ca2＋］i was determined by Fluo-3/AM, the injury of cells was observed by scanning electron microscopy (SEM).RESULTS: oxHDL could induce the expression of MCP-1 and ICAM-1 in HUVECs. In oxHDL group (HUVECs were incubated with 100 mg protein/L oxHDL for 24 h), the levels of MCP-1, ICAM-1 and ［Ca2＋］i increased by 160%, 60% and 70% respectively compared with the control group (P＜0.01). When HUVECs were incubated with 300 mg protein/L oxHDL for 24 h, cells were injured obviously. CONCLUSION: By inducing the expression of ICAM-1 and MCP-1 in endothelial cells, oxHDL may promote monocyte-endothelium adhesion and monocyte migration to intima, it may promote atherosclerosis as oxidized low-density lipoprotein (oxLDL).
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AIM: To investigate the effects of oxidized high-density lipoprotein (oxHDL) on membrane fluidity and the expression of lymphocyte function associated antigen(LFA-1) of monocyte. METHODS: The membrane fluidity of THP-1 cells was assayed by fluorescence anisotropy with DPH (1,6-dipheny-1,3,5-hexatriene), a fluorescent probe; The LFA-1 expression on THP-1 cells were assayed by flow cytometry with indirect immunofluorescence.RESULTS: The membrane fluidity of THP-1 cells was reduced by 45% and 52% respectively ( P
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AIM: To study the effects of oxidized high-density lipoprotein (oxHDL) on the expression of monocyte chemoattractant protein-1(MCP-1) and intercellular adhesion molecule-1(ICAM-1) and intracellular free calcium concentration ([Ca 2+ ]i) level in cultured human umbilical venous endothelial cells(HUVECs). METHODS: The MCP-1 protein content in the medium of conditioned HUVEC was measured by ELISA, and the ICAM-1 on HUVECs was detected by indirect immunofluorescence, and [Ca 2+ ]i was determined by Fluo-3/AM, the injury of cells was observed by scanning electron microscopy (SEM).RESULTS: oxHDL could induce the expression of MCP-1 and ICAM-1 in HUVECs. In oxHDL group (HUVECs were incubated with 100 mg protein/L oxHDL for 24 h), the levels of MCP-1, ICAM-1 and [Ca 2+ ]i increased by 160%, 60% and 70% respectively compared with the control group ( P