Animals ; Arteritis ; complications ; immunology ; Coronary Artery Disease ; etiology ; pathology ; Coronary Vessels ; pathology ; Models, Animal ; Rabbits

The concept that atherosclerosis is an inflammation has been increasingly recognized, and subsequently resulted in great interest in revealing the inflammatory nature of the atherosclerotic process. More recently, a large body of evidence has supported the idea that inflammatory mechanisms play a pivotal role throughout all phases of atherogenesis, from endothelial dysfunction and the formation of fatty streaks to plaque destabilization and the acute coronary events due to vulnerable plaque rupture. Indeed, although triggers and pathways of inflammation are probably multiple and vary in different clinical entities of atherosclerotic disorders, an imbalance between anti-inflammatory mechanisms and pro-inflammatory factors will result in an atherosclerotic progression. Vascular endothelial dysfunction and lipoprotein retention into the arterial intima have been reported as the earliest events in atherogenesis with which inflammation is linked. Inflammatory has also been extended to the disorders of coronary microvasculature, and associated with special subsets of coronary artery disease such as silent myocardial ischemia, myocardial ischemia-reperfusion, cardiac syndrome X, variant angina, coronary artery ectasia, coronary calcification and in-stent restenosis. Inflammatory biomarkers, originally studied to better understand the pathophysiology of atherosclerosis, have generated increasing interest among researches and clinicians. The identification of inflammatory biomarkers and cellular/molecular pathways in atherosclerotic disease represent important goals in cardiovascular disease research, in particular with respect of the development of therapeutic strategies to prevent or reverse atherosclerotic diseases.
Atherosclerosis ; immunology ; metabolism ; Coronary Artery Disease ; immunology ; metabolism ; Humans ; Inflammation ; metabolism ; physiopathology

OBJECTIVE: To determine the relationship between the number,phenotype and functional status of dendritic cells (DCs) and coronary collateral circulation (CCC) in coronary heart disease (CHD). METHODS: Forty patients with severe coronary stenosis were recruited and divided into a CCC formation group (Group A, n=22) and a non-CCC formation group (Group B, n=18). Density gradient centrifugation was applied to separate the mononuclear cells (MNCs) from coronary artery blood samples, and MNCs were cultured and proliferated in vitro. The morphology of DCs was observed under converted microscope. The number of harvested cells and DCs was counted by hematocytometer. Flow cytometry was applied to investigate the phenotype and the mean fluorescence intensity (MFI). Mixed lymphocyte reaction was used to test the function of DCs to stimulate the proliferation of T lymphocytes. Stimulation index (SI) was calculated and compared. RESULTS: (1) After in vitro proliferation, DCs were cultured successfully from the mononuclear cells from coronary artery blood samples and the morphology of DCs was not different in the 2 groups. (2) The number of mononuclear cells (MNC no) was (3.95+/-1.41)*10(6), in the CCC group and (2.76+/-0.92)*10(6) in the non-CCC group. The MNC number was significantly increased in the CCC group (P=0.003). (3) The number of DCs was (1.54+/-0.96)*10(6) in the CCC group, and (0.99+/-0.46)*10(6) in the non-CCC group (P=0.033). (4)There was no statistical significance in the percent of CD1a+, CD1a+CD80+, CD1a+CD83+, CD1a+CD86+ cells, and MFI in the 2 groups (P>0.05). (5) SI was 4.96+/-2.30 in the CCC group, whereas 2.66+/-1.04 in the non-CCC group. The SI in the CCC group increased significantly(P=0.0003). CONCLUSION In CHD patients with severe coronary stenosis, patients with CCC formation have higher number of DCs and stronger potential of T lymphocyte stimulation.
Aged ; Cells, Cultured ; Collateral Circulation ; immunology ; physiology ; Coronary Circulation ; immunology ; physiology ; Coronary Disease ; blood ; immunology ; physiopathology ; Coronary Stenosis ; blood ; immunology ; physiopathology ; Dendritic Cells ; immunology ; Female ; Humans ; Male ; Middle Aged ; T-Lymphocytes ; cytology ; immunology

OBJECTIVETo study the quantitative and functional changes of peripheral blood dendritic cells (DCs) and their subsets in the leukocyte population in patients with coronary artery disease (CHD) with different coronary artery plaques and explore the relation between DCs and coronary plaque development.

METHODSThirty CHD patients were divided into SAP (10 cases), UAP (10 cases) and ACS (10 cases) groups, with another 10 patients having negative result in coronary angiography as the control group. Intravascular ultrasound (IVUS) was performed to identify the nature of the plaques. The percentage and absolute number of peripheral blood DCs and DC subsets were measured by flow cytometry. The functional status of the DCs was analyzed by enzyme-linked immunosorbent assay (ELISA) and flow cytometry.

RESULTSIn the SAP group, IVUS found stable plaques in 8 cases and unstable plaques in 2 cases; in UAP group, 7 patients had unstable plaques, 2 had stable plaques, and 1 had plaque rupture. Plaque rupture, unstable plaques and stable plaques were found in 6, 3 and 1 patients in ACS group, respectively. In comparison with patients with stable plaques, those with unstable plaques had significantly increased percentages and number of DCs, mDCs and mDC1 (P<0.05), while the mDC2s and pDCs showed no obvious difference between them (P>0.05). The percentages and number of DCs, mDCs, mDC1s and pDCs were significantly decreased in patients with ruptured plaques (P<0.05). In peripheral blood monouclear cells cultured for 7 days, the CD83 expression was significantly higher in unstable and rupture plaque groups than in stable plaque group, and no significant difference was found between stable plaque group and the control group (P>0.05). In unstable and rupture plaque groups, co-culture with 2x10(5)/ml DCs evoked strong proliferation of the T cells in comparison with the stable plaque group, but no difference was found between the stable plaque and the control groups (P>0.05). Significantly higher levels of interleukin-2 and interferon-alpha were detected in the supernatant of the mixed lymphocyte reaction in unstable and ruptured plaque groups than in stable plaque and control groups, without obvious difference between the latter two groups.

CONCLUSIONThe percentage and absolute number of peripheral blood DCs and their functional status suggest the alterations of the coronary artery plaques in CHD patients.

Case-Control Studies ; Cells, Cultured ; Coronary Angiography ; Coronary Artery Disease ; immunology ; pathology ; Coronary Vessels ; pathology ; Dendritic Cells ; classification ; cytology ; immunology ; Female ; Flow Cytometry ; Humans ; Male

This review addresses the importance of psychoneuroimmunology (PNI) studies in understanding the role of acute and chronic psychological stressors on the immune system and development of coronary artery disease (CAD). Firstly, it illustrates how psychological stressors change endothelial function and lead to chemotaxis. Secondly, acute psychological stressors lead to leukocytosis, increased natural killer cell cytotoxicity and reduced proliferative response to mitogens while chronic psychological stressors may lead to adverse health effects. This will result in changes in cardiovascular function and development of CAD. Thirdly, acute and chronic psychological stressors will increase haemostatic factors and acute phase proteins, possibly leading to thrombus formation and myocardial infarction. The evidence for the effects of acute and chronic psychological stress on the onset and progression of CAD is consistent and convincing. This paper also highlights potential research areas and implications of early detection of immunological changes and cardiovascular risk in people under high psychological stress.
Acute-Phase Proteins ; Coronary Artery Disease ; immunology ; psychology ; Humans ; Inflammation ; psychology ; Myocardial Infarction ; immunology ; psychology ; Stress, Psychological ; immunology ; Thrombosis ; immunology ; psychology

UNLABELLEDTo investigate the effect of immune response mediated by the T cells stimulated with the specific antigen (oxidized low-density lipoprotein, oxLDL) on plaque stability in coronary heart disease.

METHODSThis study involved 20 patients with acute myocardial infarction (AMI), 34 with unstable angina pectoris (UAP), 27 with stable angina pectoris (SAP) and 22 healthy control subjects. With MTS/PMS colorimetric assay, the T cells from all the subjects were tested for proliferative response to stimulation by 5 microg/ml oxLDL and 5 microg/ml low-density lipoprotein (LDL). Interferon-gamma (IFN-gamma) concentration in the proliferative response of the T cells was measured with enzyme-linked immunosorbent assay (ELISA).

RESULTSThe proliferative response of the T cells elicited by 5 microg/ml oxLDL stimulation was significantly higher in the AMI and UAP groups than in the SAP and control groups (P<0.05). Similarly, IFN-gamma concentration in the proliferative response of the T cells to 5 microg/ml oxLDL stimulation was significantly higher in the former two groups (P<0.05). In the AMI and UAP groups, 5 microg

CONCLUSIONThe immune response mediated by the T cells to specific antigen stimulation, especially the immune response mediated by T helper type 1 (Th1) cells secreting IFN-gamma, may play an important role in the plaque instability and the occurrence of acute coronary syndrome.

Aged ; Coronary Disease ; immunology ; Female ; Humans ; Interferon-gamma ; secretion ; Lipoproteins, LDL ; immunology ; Male ; Middle Aged ; T-Lymphocytes ; immunology ; metabolism ; T-Lymphocytes, Helper-Inducer ; immunology ; metabolism

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 ; Angina, Unstable/*blood/*immunology ; Antibody Formation ; Autoantibodies/*analysis ; Coronary Disease/immunology ; Female ; Human ; Lipoproteins, LDL/*drug effects/*immunology ; Male ; Malondialdehyde/*pharmacology ; Middle Age

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

BackgroundAcute coronary syndrome (ACS) is closely related to unstable plaques and secondary thrombosis. The inflammatory cells in plaques and their inflammatory products may be the cause for plaque instability and ruptures. The study aimed to disclose the changes of inflammatory factors including serum intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40), and lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with ACS and its clinical significance.

MethodsA total of 120 patients with coronary heart disease (CHD) were categorized into 2 groups: 69 with ACS and 51 with stable angina pectoris (SAP); 20 patients with chest pain and normal angiography served as a control group. The 120 patients with CHD were categorized into single-vessel disease group, double-vessel disease group, and three-vessel disease group based on the number of coronary artery stenosis. The severity of coronary artery stenosis was quantified based on coronary angiography using Gensini score. They were further divided into mild CHD group with its Gensini score <26 (n = 36), moderate CHD group with its Gensini score being 26-54 (n = 48) and severe CHD group with its Gensini score >54 (n = 36). Serum levels of ICAM-1, YKL-40, and Lp-PLA2 of different groups were determined by enzyme-linked immunosorbent assay. Correlation between ICAM-1, YKL-40, Lp-PLA2, and Gensini score was analyzed.

ResultsThe levels of serum inflammatory factors ICAM-1, YKL-40, and Lp-PLA2 were significantly higher in the ACS group than those in control group and SAP group (all P < 0.05); and compared with control group, no significant difference was observed in terms of the serum ICAM-1, YKL-40, and Lp-PLA2 levels in the SAP group (P > 0.05).The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, single-vessel disease group, double-vessel disease group, and three-vessel disease group (all P > 0.05). The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, mild CHD group (Gensini score <26), moderate CHD group (Gensini score 26-54), and severe CHD group (Gensini score >54) (all P > 0.05). Nonparametric Spearman correlation analysis showed that the levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not correlated with the Gensini score in CHD patients (r = 0.093, r = -0.149, and r = -0.085, all P > 0.05; respectively).

ConclusionsThe serum levels of ICAM-1, YKL-40, and Lp-PLA2 were correlated with different clinical types of CHD, but not well correlated the severity and extent of artery stenosis, suggesting that ICAM-1, YKL-40, and Lp-PLA2 might be involved in occurrence of instability of atherosclerotic plaque, and might reflect the severity of CHD mostly through reflecting the plaque stability.

1-Alkyl-2-acetylglycerophosphocholine Esterase ; metabolism ; Acute Coronary Syndrome ; blood ; immunology ; metabolism ; Adult ; Aged ; Chitinase-3-Like Protein 1 ; metabolism ; Coronary Angiography ; Coronary Disease ; blood ; immunology ; metabolism ; Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; Middle Aged

OBJECTIVETo investigate the proinflammatory cytocine factors in patients with coronary artery disease by different treatments during perioperation.

METHODSTNF-alpha, IL-6, c-reactive protein (CRP) were measured in 37 patients with coronary artery disease (CAD) and 10 patients with mitral valve replacement (MVR, control group) before operation and aortic clamping or before coronary artery bypass grafting (CABG) in the patients with cardiopulmonary bypass, or before transmyocardial laser reperfusion (TMLR), when aortic declamping and 3, 6, 24 hours after operation.

RESULTSThe level of proinflammatory factors increased more significantly after operation than before operation. TNF-alpha increased more significantly in the patients with CPB than in those without CPB after operation [(4.10 +/- 0.71) pg/ml vs. (1.34 +/- 0.29) pg/ml, P < 0.05)]. IL-6 was not the different among all groups after operation. CRP was higher in the CAD patients with CPB than in the control group after operation [(12.89 +/- 0.29) pg/ml vs. (12.00 +/- 0.31) pg/ml, P < 0.05].

CONCLUSIONInflammatory response can be seen after operation in all CAD patients. In patients undergoing CABG without CPB or undergoing TMLR, the changes in flammatory response are milder than those in patients with CPB. Thus patients should undergo CABG without CPB if they are indicated.

Aged ; C-Reactive Protein ; analysis ; Cardiopulmonary Bypass ; Coronary Artery Bypass ; Coronary Disease ; immunology ; surgery ; Female ; Humans ; Interleukin-6 ; blood ; Male ; Middle Aged ; Tumor Necrosis Factor-alpha ; analysis