1.Autoantibody against, Malondialdehyde-Modified Low Density Lipoprotein in Patients with Non-Diabetic Unstable Angina: A Potential Role in Immunologic Reaction of Plaque Instability.
Ki Hwan KWON ; Hyuck Moon KWON ; Bum Kee HONG ; Dong Soo KIM ; Ju Yong LEE ; Sung Kee RYU ; Byoung Eun PARK ; Hyun Young PARK ; Jeong Ho KIM ; Young Won YOON ; Seung Yun CHO ; Hyun Seung KIM
Yonsei Medical Journal 2002;43(2):203-210
The role of autoantibody against oxidized low-density lipoprotein (LDL) in the pathogenesis of atherosclerosis is still unknown. The purpose of this study was to determine whether autoantibodies against malondialdehyde (MDA)-modified LDL are associated with coronary artery disease (CAD) and clinical presentations of CAD in non-diabetic patients without acute myocardial infarction (AMI). We determined the serum levels of autoantibody against MDA-modified LDL by ELISA in 71 patients with angiographically significant CAD (> or = 50% diameter stenosis in at least 1 vessel) and 80 controls without angiographically significant CAD. Among the total 151 subjects, 30 subjects did not have any clinical ischemic event, 90 subjects had stable angina symptoms, and 31 subjects had unstable angina symptoms. The autoantibody titer, expressed mean optical density units, was significantly higher in patients with CAD than in controls (0.177+/- 0.014 versus 0.127+/- 0.011, respectively; p=0.006) and higher in unstable angina group than in stable angina group (0.240+/- 0.025 versus 0.145+/- 0.007, respectively; p < 0.001). By logistic regression analysis, the high autoantibody titer was associated significantly with CAD (P=0.008), independent of age, gender, body mass index, triglyceride concentration, and the ratio of total cholesterol-high density lipoprotein (HDL) cholesterol. In multiple regression analysis, presence of CAD, smoking history and low HDL-cholesterol level were independent factors associated with a increased anti-oxLDL Ab titer. The autoantibody titer was significantly lower in nonsmoker than smoker (p=0.019) and higher in low HDL- cholesterol (< or = 35 mg/dl) group than in high HDL-cholesterol group (p=0.012). Elevated autoantibody titer was associated with CAD and the unstable clinical presentation of CAD. Our results suggest that immune response to oxidized LDL may play a role in the pathogenesis of atherosclerosis and plaque instability.
Aged
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Angina, Unstable/*blood/*immunology
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Antibody Formation
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Autoantibodies/*analysis
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Coronary Disease/immunology
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Female
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Human
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Lipoproteins, LDL/*drug effects/*immunology
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Male
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Malondialdehyde/*pharmacology
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Middle Age
2.Activation of monocytes, T-lymphocytes and plasma inflammatory markers in angina patients.
Won Ha LEE ; Yoon LEE ; Jong Ran KIM ; Jin A CHU ; Sung Youn LEE ; Jin Ok JUNG ; Joon Soo KIM ; Seonwoo KIM ; Jung Don SEO ; Sung S RHEE ; Jeong Euy PARK
Experimental & Molecular Medicine 1999;31(3):159-164
Inflammation and activation of immune cells have important roles in the pathogenesis of atherosclerosis. We analyzed the plasma levels of inflammatory markers and the degree of activation of peripheral blood monocytes and T-lymphocytes isolated from 12 unstable angina, 12 stable angina, and 12 normal subjects. In 20%-33% of patients, monocytes expressed high basal levels of IL-8, tissue factor, IL-1beta, and monocyte chemoattractant protein-1 mRNA. Furthermore, basal mRNA levels of these cytokines showed strong correlation with each other (p < 0.01 in all combination) but not with tumor necrosis factor-alpha or transforming growth factor-beta1. Plasma level of C-reactive protein was highest in the unstable angina patients (1.63+/-0.70 mg/l) and lowest in the control subjects (0.22+/-0.08 mg/l) (P = 0.03). We also observed a high correlation between C-reactive protein level and the occurrence of minor and major coronary events during 6 months of follow-up. Activation status of T-cells, assessed by the percentage of HLA-DR positive cells, was highest in the unstable angina patients (26.8+/-1.4%) compared with that in the control (14.7+/-1.2%) (P = 0.0053). Our data represent the first case showing that the circulating monocytes in angina patients are activated to a state express numerous proatherogenic cytokines. These results may help to diagnose angina patients according to the inflammatory markers and evaluate the prognosis of the disease.
Aged
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Angina Pectoris/immunology*
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Angina Pectoris/diagnosis
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Angina, Unstable/immunology*
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Angina, Unstable/diagnosis
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Biological Markers/blood
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C-Reactive Protein/analysis
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Cytokines/blood*
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Female
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HLA-DR Antigens/immunology
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Human
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Interleukins/blood
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Lymphocyte Transformation
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Male
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Middle Age
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Monocyte Chemoattractant Protein-1/blood
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Monocytes/metabolism*
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RNA, Messenger/metabolism
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T-Lymphocytes/metabolism*
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Transforming Growth Factor beta/analysis
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Tumor Necrosis Factor/analysis
4.Immunologic mechanisms and treatment of acute coronary syndromes.
Ying LIU ; Yu-hua LIAO ; Xiang CHENG
Chinese Medical Journal 2006;119(24):2108-2113
5.Changes of CD4+CD28- T cell and CD4+CD25+ regulatory T cell subsets in patients with coronary heart disease.
Yi-qiao ZHAO ; Qiang FU ; Zhi-liang LI ; Quan-neng YAN ; Hong-chao WU ; Fei MIAO ; Yong-heng LÜ ; Ying-feng LIU
Journal of Southern Medical University 2007;27(4):474-476
OBJECTIVETo investigate the changes of CD4(+)CD28(-) T cell and CD4(+)CD25(+) regulatory T cell (Treg) subsets in patients with coronary artery disease (CAD).
METHODSTwenty-eight patients with angiographically established CAD were recruited in this study, including 16 with unstable angina (UA group) and 12 with stable angina (SA group). Eleven patients with chest pain syndrome served as the control group. The proportions of peripheral CD4(+)CD28(-) T cells and CD4(+)CD25(+) Treg subsets were determined with fluorescence-activated cell sorting (FACS).
RESULTSThe proportions of CD4(+)CD25(+) Treg were significantly lower in UA group (6.55-/+2.45%) than in SA (14.01-/+4.92%) and control groups (13.55-/+3.87%). The proportions of CD4(+)CD28(-) T cells were significantly higher in UA group (10.55-/+4.76%) than in SA (2.64-/+1.33%) and control (2.75-/+1.55%) groups.
CONCLUSIONAlterations of circulating T-lymphocyte subsets occur in patients with UA. The changes of Treg and CD4(+)CD28(-) T cells may lead to breakdown of peripheral autoimmune tolerance and play an important role in the development and progression of CHD.
Aged ; Angina, Unstable ; immunology ; CD28 Antigens ; CD4-Positive T-Lymphocytes ; immunology ; Case-Control Studies ; Coronary Disease ; immunology ; Female ; Humans ; Interleukin-2 Receptor alpha Subunit ; Male ; Middle Aged ; T-Lymphocyte Subsets ; immunology ; T-Lymphocytes, Regulatory ; immunology
6.Measurement peripheral blood index related to inflammation and ox-LDL, ox-LDLAb in patients with coronary heart disease and its clinical significance.
Zhao-xia ZHOU ; Hua QIANG ; Ai-Qun MA ; Hua CHEN ; Ping ZHOU
Journal of Central South University(Medical Sciences) 2006;31(2):258-262
OBJECTIVE:
To detect the levels of index related to inflammation such as soluble CD40 ligand (sCD40L), neutrophil collagenase-8 (MMP-8), and pregnancy associated plasma protein-A (PAPP-A) , lipid peroxidation and autoimmune indexes such as oxidized low density lipoprotein (ox-LDL) and its antibody (ox-LDL Ab) in patients with coronary heart disease, and to investigate its relationship with acute coronary syndrome (ACS).
METHODS:
Contents of sCD40L, MMP-8, PAPP-A, ox-LDL and ox-LDL Ab in the peripheral blood were measured by enzyme-linked immunosorbent assay from 109 patients with coronary heart disease including 36 acute myocardial infarction (AMI), 38 unstable angina pectoris (UAP), and 35 stable angina pectoris (SAP) and 36 controls without coronary heart disease.
RESULTS:
The levels of each index in the peripheral blood of ACS patients (including AMI and UAP) were higher than those of SAP patients and controls (P < 0.05), and the difference of each index between UAP group and AMI group in ACS patients had no statistical significance (P > 0.05). The levels of each index of SAP patients, except PAPP-A, were all higher than those of controls (P <0.05). All the indexes were helpful in diagnosis of ACS. The area under the ROC curve of each index is between 0.7 and 0.9.
CONCLUSION
The increase of sCD40L, MMP-8, PAPP-A, ox-LDL and ox-LDL Ab levels in peripheral blood may be related to the pathogenesis of ACS, and can be used as potential markers of unstable atherosclerosis plaque.
Aged
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Angina, Unstable
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blood
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immunology
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Autoantibodies
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blood
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Biomarkers
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blood
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CD40 Ligand
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blood
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Coronary Artery Disease
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blood
;
immunology
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Female
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Humans
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Lipoproteins, LDL
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blood
;
immunology
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Male
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Matrix Metalloproteinase 8
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blood
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Middle Aged
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Myocardial Infarction
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blood
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immunology
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Pregnancy-Associated Plasma Protein-A
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metabolism
7.Effect of immune response mediated by antigen-specific T cells on plaque stability in coronary heart disease.
Hua ZHENG ; Yan TU ; Zhong-hua TENG
Journal of Southern Medical University 2010;30(7):1610-1614
OBJECTIVETo investigate the effect of immune response mediated by antigen (oxidized low density lipoprotein, oxLDL)-specific T cells on plaque stability in coronary heart disease.
METHODSTwenty patients with acute myocardial infarction (AMI), 34 with unstable angina pectoris (UAP), 27 with stable angina pectoris (SAP) and 22 control subjects were enrolled in this study. MTS/PMS colorimetric assay was used to measure the proliferative response of the T cells to stimulation to 5 microg/ml oxLDL and detect IFN-gamma concentration produced in the proliferative response. The effect of C-reactive protein (CRP) on the proliferative response of the T cells to oxLDL and IFN-gamma concentration produced was examined in AMI group and UAP group.
RESULTSThe proliferative response of T cells to stimulation to 5 microg/ml oxLDL was significantly higher in AMI group and UAP group than in SAP group and the control group (P<0.05). IFN-gamma concentration produced in the proliferative response of the T cells was also significantly higher in AMI group and UAP group than in the other two groups (P<0.05). CRP at 10 microg/ml significantly increased the proliferative response of the T cells to oxLDL and IFN-gamma production in ACS group (P<0.001).
CONCLUSIONThe immune response mediated by the antigen-specific T cells, especially that mediated by type 1 T helper cells secreting IFN-gamma, may play an important role in the instability of plaques, and CRP may promote the inflammation of atherosclerosis through the effects on the specific immune response to oxLDL.
Aged ; Angina Pectoris ; immunology ; metabolism ; pathology ; Angina, Unstable ; immunology ; metabolism ; pathology ; C-Reactive Protein ; metabolism ; Case-Control Studies ; Coronary Disease ; immunology ; metabolism ; pathology ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; immunology ; metabolism ; pathology ; Plaque, Atherosclerotic ; immunology ; metabolism ; pathology ; T-Lymphocytes ; metabolism
8.Effects of Ginkgo leaf extract on function of dendritic cells and Th1/Th2 cytokines in patients with unstable angina pectoris.
Da-zhu LI ; Ranjit SHARMA ; Qiu-tang ZENG
Chinese journal of integrative medicine 2005;11(4):260-263
OBJECTIVETo investigate the effects of Ginkgo leaf extract (GLE) on function of dendritic cells (DC) and Th1/Th2 cytokines in patients with unstable angina pectoris (UAP).
METHODSFifty-four patients with UAP were equally assigned into two groups, the treated group and the control group, both treated with conventional Western medicine, but with GLE given additionally to the treated group. Blood of all patients was taken before and 4 weeks after treatment to prepare the peripheral mononuclear cells, then which were incubated in the completed medium containing granulocyte-macrophage colony stimulatory factor (GM-CSF) and interleukin-4 (IL-4) to induce mature DC. The expression of co-stimulating factor CD86 (B7-2) on the surface of DC was detected by flow cytometry, and the stimulating capacity of DC was determined by mixed lymphocyte reaction (MLR). The blood levels of cytokines, interferon-gamma (IFN-gamma), and IL-4, were analyzed by ELISA, and blood C-reactive protein (CRP) level by turbidimetry. Moreover, the direct effect of Ginkgolide B on CD86 expression on DC were also tested in vitro.
RESULTSAfter treatment, CD86 expression on DC, the stimulating capacity of DC as well as levels of IFN-gamma and CRP were lowered in both groups (P < 0.05 or P < 0.01), but the changes were much more significant in the treated group than those in the control group. Ginkgolide B showed a direct inhibitory effect on the CD86 expression on DC.
CONCLUSIONThe inhibition of GLE on DC and thereby the suppression on inflammatory reaction may be one of the mechanisms of GLE in treating patients with UAP.
Adult ; Aged ; Angina, Unstable ; immunology ; B7-2 Antigen ; analysis ; C-Reactive Protein ; analysis ; Cells, Cultured ; Dendritic Cells ; cytology ; drug effects ; immunology ; Diterpenes ; pharmacology ; Female ; Ginkgolides ; Humans ; Interferon-gamma ; analysis ; Interleukin-4 ; analysis ; Lactones ; pharmacology ; Male ; Middle Aged
9.Effect of compound paeonol dripping pill on levels of plasma inflammatory mediators in patients with unstable angina.
Chinese Journal of Integrated Traditional and Western Medicine 2008;28(5):395-398
OBJECTIVETo evaluate the clinical therapeutic effect of Compound Paeonol Dripping Pill (CPDP) and its effect on the levels of plasma inflammatory mediators, including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and monocyte chemotactic protein-1 (MCP-1).
METHODSNinety patients with unstable angina were randomized by enveloping method into 3 groups equally, the conventional Western therapy group (A), the CPDP group (B), and the Tongxinluo group (C). The improvement of angina pectoris symptoms and electrocardiogram (ECG) was observed after 2 weeks of treatment and the levels of plasma CRP, IL-6, TNF-alpha and MCP-1 were measured before and after treatment.
RESULTSThe total effective rate in improving angina pectoris was 93.3% in Group B, significantly higher than that in Group A (73.3%, P <0.01) and Group C (76.7%, P <0.05), while no significant difference of ECG improvement rate was found between the three groups (P >0.05). Plasma total cholesterol and inflammation indexes were significantly lowered after treatment in Group B (P <0.05), showing a significant difference to those in the other two groups (P <0.05), but the indexes were unchanged in the other two groups (P >0.05).
CONCLUSIONEffect of CPDP is better in relieving symptoms, depressing inflammatory reaction for treatment of unstable angina patients than that of Tonxinluo Capsule and conventional Western treatment.
Acetophenones ; administration & dosage ; therapeutic use ; Angina, Unstable ; drug therapy ; immunology ; C-Reactive Protein ; metabolism ; Chemokine CCL2 ; blood ; Humans ; Inflammation Mediators ; blood ; Interleukin-6 ; blood ; Tablets ; Tumor Necrosis Factor-alpha ; blood
10.Study on effect of promoting blood circulation drugs components in treating unstable angina in patients with blood stasis inflammatory levels.
Xian LIU ; Ji LI ; Ge YANG ; Jie WANG
China Journal of Chinese Materia Medica 2008;33(24):2950-2953
OBJECTIVETo discussion the effects of Huoxue components of effective drug in treating unstable angina in patients with blood stasis WBC (WBC), C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha).
METHODone hundred and twenty cases of unstable angina were randomly divided into the conventional therapy group, component compatibility group, Pieces group and Xuesaitong group 4 groups, each with 30 cases. Observation of patients before and after treatment of clinical efficacy, blood lipid indicators and the indicators changes.
RESULTComponent compatibility group after treatment clinical marked improvement in conditions, and the WBC, CRP, IL-6 and TNF-alpha, TC, TG levels lower than before treatment, there were significant differences (P < 0.05), and lower than the other three groups After treatment (P < 0.05). And HDL-C after treatment than before treatment increased, there were significant differences (P < 0. 05).
CONCLUSIONHuoxue-effective component compatibility can be effective treatment of unstable angina blood stasis, and could inhibit the inflammatory level.
Aged ; Angina, Unstable ; blood ; drug therapy ; immunology ; Blood Circulation ; drug effects ; C-Reactive Protein ; immunology ; Cardiotonic Agents ; administration & dosage ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Interleukin-6 ; blood ; immunology ; Leukocytes ; drug effects ; Male ; Middle Aged ; Tumor Necrosis Factor-alpha ; blood ; immunology