3.Association between non-alcoholic fatty liver disease and coronary artery disease severity.
Chinese Medical Journal 2011;124(6):867-872
BACKGROUNDBoth non-alcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) are closely associated with many metabolic disorders. Invasive coronary angiography (CAG) is a common approach as an intervention for CAD. However, the association between angiographic severity of coronary artery and NAFLD remains controversial. This study aimed to evaluate the relationship between NAFLD and CAD.
METHODSTotally 542 consecutive patients who planned to undergo CAG due to a suspected CAD were enrolled. Abdominal computed tomography (CT) was performed before angiography to detect NAFLD. CAD was defined as stenosis of at least 50% in at least one major coronary artery. The severity of CAD was assessed by the number of vessels affected and the vessel score multiplied by the severity score (Gensini score). Significant stenosis was defined as 70% or greater reduction in lumen diameter. A probability value of P < 0.05 was considered statistically significant.
RESULTSOf 542 patients studied, 248 (45.8%) were found to have NAFLD by abdominal CT, and 382 patients (88%) were found to have significant CAD by CAG. Age, diabetes mellitus, waist circumference, body mass index, and obesity were associated with NAFLD. According to the results of Logistic regression analysis, the presence of NAFLD independently increased the risk for CAD, as seen in CAG (odds ratio (OR), 95% confidence interval (CI): 7.585 (4.617-12.461); P < 0.001). NAFLD was significantly more common in patients as CAD severity increased (P < 0.001).
CONCLUSIONSThe presence of NAFLD is associated with high severity of CAD, requiring that patients with abdominal obesity be also investigated for NAFLD. Patients with NAFLD should be closely followed up for the presence and severity of CAD.
Aged ; Coronary Angiography ; Coronary Artery Disease ; diagnostic imaging ; pathology ; Fatty Liver ; diagnostic imaging ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease
4.Effects of intensive antiplatelet therapy in patients with high platelet aggregability after percutaneous coronary intervention.
Yan-ling LU ; Yun-dai CHEN ; Shu-zheng LÜ
Chinese Journal of Cardiology 2007;35(9):793-796
OBJECTIVEPost percutaneous coronary intervention (PCI) major cardiac event rate is high in patients with high platelet aggregability. We observed the effects of intensive antiplatelet therapy in these patients.
METHODSADP-induced platelet inhibition rates were less than 30% after 24 h treatment with Clopidogrel (300 mg) in 402 patients out of 1556 patients who underwent PCI in our institute between January 2004 to June 2006. These patients were randomly divided into control group (Clopidogrel 75 mg/d and aspirin 100 mg/d, n = 201) or treatment group (Clopidogrel 75 mg/d and aspirin 100 mg/d plus cilostazol 200 mg/d, n = 201). Major adverse cardiac events were analyzed after 6 months treatments.
RESULTSPatients with ADP-induced platelet inhibition rates < 30% were significantly lower in treatment group compared to control group after 28 days treatments (9.4% vs. 89.6%, P < 0.05). Thrombosis complication (0.5% vs. 3.0%), death (0 vs. 1.0%), non-fatal myocardial infarction (0.5% vs. 1.5%), hemorrhagic (6% vs. 4%) rates were similar between treatment and control group while target vessel revascularization rate was significantly lower in treatment group compared to control group (6.5% vs. 15.9%, P < 0.05). Total MACE rate was therefore significantly lower in treatment group than that in control group (13.5% vs. 25.4%, P < 0.05).
CONCLUSIONIntensive anti-platelet treatment could significantly reduce major cardiac event rates in patients with high platelet aggregability after percutaneous coronary intervention.
Aged ; Angioplasty, Balloon, Coronary ; Aspirin ; therapeutic use ; Coronary Artery Disease ; drug therapy ; physiopathology ; therapy ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; therapeutic use ; Platelet Count ; Ticlopidine ; analogs & derivatives ; therapeutic use
5.Relationship between serum vasoactive factors and plaque morphology in patients with non-ST-segment elevated acute coronary syndrome.
Ya-feng LU ; Shu-zheng LÜ ; Yun-dai CHEN
Chinese Medical Journal 2010;123(2):193-197
BACKGROUNDVasoactive factors have been reported to correlate with vulnerable plaque and acute coronary syndrome (ACS). This study aimed to investigate the relationship between vasoactive factors and plaque morphology in patients suffering from non-ST-segment elevated ACS.
METHODSFrom April 2007 to April 2009, 124 consecutive patients suffering from non-ST-segment elevated ACS who had received coronary angiography (CAG) and intravascular ultrasound (IVUS) in the People's Liberation Army General Hospital and Beijing Anzhen Hospital were enrolled in this study. Three serum vasoactive factors, plasma soluble vascular endothelial growth factor receptor-1 (sFlt-1), placental growth factor (PLGF) and interleukin-18 (IL-18), were measured by enzyme-linked-immunosorbent serologic assay of the patients. The levels of vasoactive factors were compared between vulnerable plaque group and stable plaque group, and between unstable angina pectoris (UAP) group and non-ST-segment elevation acute myocardial infarction (NSTE-AMI) group. The relationship between the plaque morphology and levels of vasoactive factors was analyzed.
RESULTSThe levels of vasoactive factors were similar between the UAP group (69 patients) and NSTE-AMI group (55 patients). The levels of sFlt-1 and PLGF in the vulnerable plaque group were significantly higher than those in the stable plaque group. The level of IL-18 was correlated positively with plaque morphology. Multivariate Logistic regression analysis showed that the level of PLGF was an independent risk factor for vulnerable plaque (OR=2.115, 95% CI 1.415-5.758, P=0.018). Using the ROC curve, PLGF was a significant factor for the diagnosis of vulnerable plaque (the diagnostic point was 26.3 ng/L, the proportion of square area under the ROC curve was 0.799, 95%CI 0.758-0.839, P<0.001; the sensitivity of PLGF under the ROC curve was 86%, and the specificity 63%).
CONCLUSIONBoth IL-18 and PLGF are biomarkers for vulnerable plaques and helpful to predict vulnerable plaque.
Acute Coronary Syndrome ; blood ; diagnostic imaging ; Aged ; Angina Pectoris ; blood ; diagnostic imaging ; Angina, Unstable ; blood ; diagnostic imaging ; Coronary Angiography ; Female ; Humans ; Interleukin-18 ; blood ; Male ; Middle Aged ; Placenta Growth Factor ; Pregnancy Proteins ; blood ; Ultrasonography, Interventional ; Vascular Endothelial Growth Factor Receptor-1 ; blood
6.Relationship between plasma cathepsin S and cystatin C levels and coronary plaque morphology of mild to moderate lesions: an in vivo study using intravascular ultrasound.
Fei-fei GU ; Shu-zheng LÜ ; Yun-dai CHEN ; Yu-jie ZHOU ; Xian-tao SONG ; Ze-ning JIN ; Hong LIU
Chinese Medical Journal 2009;122(23):2820-2826
BACKGROUNDCathepsin S and its endogenous inhibitor cystatin C are implicated in the pathogenesis of atherosclerosis, especially in the plaque destabilization and rupture leading to acute coronary syndrome. However, whether circulating cathepsin S and cystatin C also change in association with coronary plaque morphology is unknown yet.
METHODSWe recruited 98 patients with unstable angina (UA, n = 6) or stable angina (SA, n = 2) who had a segmental stenosis resulting in > 20% and < 70% diameter reduction in one major coronary artery on coronary angiography. Thirty-one healthy subjects served as controls. Intravascular ultrasound (IVUS) was used to evaluate plaque morphology. Plasma cathepsin S and cystatin C were measured as well.
RESULTSAt the culprit lesion site, plaque area ((7.85 +/- 2.83) mm(2) vs (6.53 +/- 2.92) mm(2), P = 0.027), plaque burden ((60.92 +/- 11.04)% vs (53.87 +/- 17.52)%, P = 0.025), remodeling index (0.93 +/- 0.16 vs 0.86 +/- 0.10, P = 0.004) and eccentricity index (0.74 +/- 0.17 vs 0.66 +/- 0.21, P = 0.038) were bigger in UA group than in SA group. Plasma cathepsin S and cystatin C were significantly higher in patients than in controls (P < 0.01). Plasma cathepsin S was higher in UA group ((0.411 +/- 0.121) nmol/L) than in SA group ((0.355 +/- 0.099) nmol/L, P = 0.007), so did the plasma cystatin C ((0.95 +/- 0.23) mg/L in UA group, (0.84 +/- 0.22) mg/L in SA group; P = 0.009). Plasma cathepsin S positively correlated with remodeling index (r = 0.402, P = 0.002) and eccentricity index (r = 0.441, P = 0.001), and plasma cystatin C positively correlated with plaque area (r = 0.467, P < 0.001) and plaque burden (r = 0.395, P = 0.003) in UA group but not in SA group.
CONCLUSIONSPlasma cathepsin S and cystatin C increased significantly in UA patients. In angina patients, higher plasma cathepsin S may suggest the presence of vulnerable plaque, and higher plasma cystatin C may be a clue for larger atherosclerotic coronary plaque.
Adult ; Aged ; Aged, 80 and over ; Cathepsins ; blood ; Coronary Artery Disease ; blood ; diagnostic imaging ; pathology ; Cystatin C ; blood ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Ultrasonography, Interventional ; methods
7.Baicalein selectively induce apoptosis in human leukemia K562 cells.
Qing-hua DONG ; Shu ZHENG ; Rong-zhen XU ; Qing-hua LÜ
Acta Pharmaceutica Sinica 2003;38(11):817-820
AIMTo study the antitumor effect of baicalein on human leukemia K562 cell and its mechanism.
METHODSThe IC50 value and cytotoxity of K562 cell were detected by MTT method. The apoptotic cell was analyzed by FCM using Annexin V FITC--PI staining method. Sub-G1 peak was also measured by FCM. Protein expressions of Bcl-2, Fas, Caspase 3 were evaluated with FCM.
RESULTSBaicalein was shown to significantly inhibit the proliferation of K562 cell in a dose-dependent manner and selectively induce apoptosis of human leukemia K562 cells. Flow cytometric analysis showed that baicalein arrested K562 cells in the S phase. In addition, protein expression of Fas, Caspase 3 of K562 cells increased after exposure to baicalein, but Bcl-2 was unchanged.
CONCLUSIONBaicalein can selectively induce apoptosis of human leukemia K562 cell dose and time dependently through up-regulation of caspase-3 and fas gene expression level.
Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; Caspases ; metabolism ; Cell Cycle ; drug effects ; Flavanones ; Flavonoids ; pharmacology ; Humans ; K562 Cells ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Up-Regulation
8.Long-term outcome of native artery versus bypass graft intervention in prior coronary artery bypass graft patients with ST-segment elevation myocardial infarction.
Wei LIU ; Yu-Yang LIU ; Venkata K MUKKU ; Dong-Mei SHI ; Shu-Zheng LÜ ; Yu-Jie ZHOU
Chinese Medical Journal 2013;126(12):2281-2285
BACKGROUNDPatients with prior coronary artery bypass graft (CABG) have a poor outcome after acute myocardial infarction (AMI). Little is known about the treatment strategy and outcome of percutaneous coronary intervention (PCI) in these patients. The purpose of this study was to investigate the impact of graft versus native artery PCI on the outcomes of prior CABG patients with AMI.
METHODSBetween September 2005 and October 2011, a total of 140 consecutive patients with previous CABG undergoing PCI for the treatment of AMI were included. Clinical/procedural characteristics and long-term clinical outcomes were compared between graft and native artery PCI patients.
RESULTSThe mean time interval to prior CABG was (5.6 ± 4.2) years. Thirty patients received graft PCI, success rate being 90%. One hundred and ten patients received native artery PCI, success rate being 90.7% (P > 0.05). There were no significant differences in the basic characteristics between the two groups. All patients received drug eluting stents (DESs). Three patients died during hospitalization in the graft-PCI group (10% vs. native PCI 0, P < 0.05). After a median follow- up of two years, major adverse cardiac events (MACE) (myocardial infarction, target vessel revascularization, total death) were 20% with no significant difference between the two groups. Cox regression analysis showed that both diabetes mellitus (DM, HR 3.57, 95%CI 1.03 - 5.75, P < 0.05) and primary PCI (HR 5.932, 95%CI 1.91 - 18.4, P < 0.05) were independent predictors of MACE.
CONCLUSIONSMore patients with prior CABG underwent native artery PCI for AMI. PCI to culprit graft vessels had higher in-hospital mortality. DM and primary PCI, but not graft PCI, were predictors for adverse long-term outcome.
Aged ; Coronary Artery Bypass ; Electrocardiography ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; physiopathology ; surgery ; Percutaneous Coronary Intervention ; Proportional Hazards Models ; Retrospective Studies ; Treatment Outcome
9.Antithrombotic and antiplatelet therapies in relation to risk stratification in patients with non-ST elevation acute coronary syndrome: insights from the Sino-Global Registry of Acute Coronary Events.
Li-jie ZHANG ; Yun-dai CHEN ; Xian-tao SONG ; Fu-hai ZHAO ; Shu-zheng LÜ
Chinese Medical Journal 2009;122(5):502-508
BACKGROUNDAntithrombotic and antiplatelet therapies have been proposed to treat non-ST elevation acute coronary syndrome (NSTEACS), yet limited information is available about their applications from a multicenter "real-world" clinical procedure, especially in China. This study was undertaken to characterize the use of antithrombotic and antiplatelet agents in relation to the risk levels of the NSTEACS patients who were enrolled in Sino-Global Registry of Acute Coronary Events (GRACEs) registry study.
METHODSWe analyzed the data from 618 Chinese NSTEACS patients stratified into low-(n = 151), intermediate-(n = 233), and high-risk groups (n = 234) based on GRACE risk scores. The baseline characteristics, clinical presentations, antithrombotic and antiplatelet agents were recorded and compared among the three groups.
RESULTSThe administration rates of low-molecular-weight heparins (LMWHs) (86.08%) and thienopyridines (85.92%) were higher whereas the administration rate of glycoprotein IIb/IIIa inhibitor (1.78%) was much lower than those reported previously. Meanwhile, within the first 24 hours of admission, the use of heparin/LMWHs in the high-risk group was more than that in the intermediate- and low-risk groups (73.50% vs 63.09% vs 55.63%, P = 0.001). Furthermore, the combination of antithrombotic and antiplatelet medications showed no significant differences in all groups.
CONCLUSIONSIn the "real world" practice of China, the antithrombotic and antiplatelet therapies on NSTEACS are well adherent to the current guidelines except for several gaps, such as the very low use of glycoprotein IIb/IIIa inhibitor. Moreover, these antithrombotic and antiplatelet treatments usually tend to be underused for the high-risk ones.
Acute Coronary Syndrome ; drug therapy ; Aged ; Coronary Disease ; drug therapy ; Female ; Fibrinolytic Agents ; therapeutic use ; Heparin, Low-Molecular-Weight ; therapeutic use ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors ; therapeutic use ; Platelet Glycoprotein GPIIb-IIIa Complex ; antagonists & inhibitors ; Pyridines ; therapeutic use ; Registries ; Risk Assessment
10.Target-specific cytotoxic activity of recombinant fusion toxin C-CPE-ETA' against CLDN-3,4-overexpressing ovarian cancer cells.
Qin YAO ; Qing-Mei ZHENG ; Jun-Feng WEN ; Teng LÜ ; Ming-Qian WEI ; Shu-Zhen DAI
Chinese Journal of Oncology 2010;32(12):897-902
OBJECTIVEThe aim of this study was to explore the possibility of creating a toxin, C-CPE-ETA', by fusing C-terminal high affinity binding domain of CPE (C-CPE) with a truncated form of Pseudomonas aeruginosa exotoxin A (ETA') and to examine whether C-CPE-ETA' could specifically target CLDN-3, 4 molecule and the targeted toxin was cytotoxic against CLDN-3,4-overexpressing ovarian cancer.
METHODSCLDN-3 and CLDN-4 expressions were analyzed at the mRNA level in three ovarian cancer cell lines and epithelial ovarian cancer tissues from 20 patients. After transforming an expression plasmid of C-CPE-ETA' into E. coli BL21 (DE3) plysS strain, the recombinant protein was purified using His-Bind resin chromatography column and analyzed by Western blot and Coomassie blue staining. The specific binding, proapoptotic and cytolytic activities were evaluated by flow cytometry, fluorescence microscopy with the JC-1 probe and MTT assay in CLDN-3,4-overexpressing ovarian cancer cells.
RESULTSQuantitive RT-PCR results showed there existed high levels of CLDN-3 and CLDN-4 in ovarian cancer cells, CAOV3, OVCAR3 and SKOV3. Moreover, high expressions of CLDN-3 and CLDN-4 were observed in 90.0% (18/20) and 60.0% (12/20) of ovarian cancer tissues, with an expression level 10-fold higher than that in the normal ovarian tissue. A 58 000 recombinant protein C-CPE-ETA' was demonstrated by Western blot and Coomassie blue staining. Purified and recombinant C-CPE-ETA' was bound with high affinity to CLDN-3,4-overexpressing ovarian cancer cells, CAOV3, OVCAR3 and SKOV3 cells. C-CPE-ETA' was strongly proapoptotic and cytotoxic towards the CLDN-3,4-overexpressing ovarian cancer cells. The concentration of IC(50) was 7.364 ng/ml for CAOV3 cells, 8.110 ng/ml for OVCAR3 cells and 22.340 ng/ml for SKOV3 cells, respectively. However, control CLDN-3,4-deficient cell line HUVEC was not susceptible to the recombinant C-CPE-ETA' at a concentration up to 10 µg/ml.
CONCLUSIONSThe C-CPE-ETA' protein exhibits remarkably specific cytotoxicity for CLDN-3,4-overexpressing ovarian cancer cells. Its therapeutic potential warrants further development for ovarian cancer molecular targeted therapy.
ADP Ribose Transferases ; metabolism ; physiology ; Apoptosis ; Bacterial Toxins ; metabolism ; Cell Line, Tumor ; Claudin-3 ; Claudin-4 ; Claudins ; genetics ; metabolism ; Enterotoxins ; metabolism ; physiology ; Exotoxins ; metabolism ; physiology ; Female ; Humans ; Immunotoxins ; metabolism ; Ovarian Neoplasms ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Recombinant Fusion Proteins ; metabolism ; physiology ; Virulence Factors ; metabolism ; physiology