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

PURPOSE: Elastin is a major arterial structural protein, and elastin-derived peptides are related to arterial change. We previously reported on a novel assay developed using aortic elastin peptides; however, its clinical implications remain unclear. In this study, we assessed whether anti-elastin antibody titers reflect the risk of coronary artery disease (CAD) or its characteristics. MATERIALS AND METHODS: We included 174 CAD patients and 171 age- and sex-matched controls. Anti-elastin antibody titers were quantified by enzyme-linked immunosorbent assay. Parameters of arterial stiffness, including the augmentation index (AI) and heart-to-femoral pulse wave velocity (hfPWV), were measured non-invasively. The clinical and angiographic characteristics of CAD patients were also evaluated. Associations between anti-elastin levels and vascular characteristics were examined by linear regression analysis. RESULTS: The median blood level of anti-elastin was significantly lower in the CAD group than in the controls [197 arbitrary unit (a.u.) vs. 63 a.u., p<0.001]. Levels of anti-elastin were significantly lower in men and in subjects with hypertension, diabetes mellitus, hyperlipidemia, or high hfPWV. Nevertheless, anti-elastin levels were not dependent on atherothrombotic events or the angiographic severity of CAD. In a multivariate analysis, male sex (beta=-0.38, p<0.001), diabetes mellitus (beta=-0.62, p<0.001), hyperlipidemia (beta=-0.29, p<0.001), and AI (beta=-0.006, p=0.02) were ultimately identified as determinants of anti-elastin levels. CONCLUSION: Lower levels of anti-elastin are related to CAD. The association between antibody titers and CAD is linked to arterial stiffness rather than the advancement of atherosclerosis.
Aged ; Angiography ; Antibodies/*blood ; Atherosclerosis/*blood/immunology ; Coronary Artery Disease/blood/*immunology ; Elastin/*blood/immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Hyperlipidemias ; Hypertension/complications ; Male ; Middle Aged ; Pulse Wave Analysis ; Vascular Stiffness/*immunology/physiology

We investigated the persistence of viable Orientia tsutsugamushi in patients who had recovered from scrub typhus. Blood specimens were available from six patients with scrub typhus who were at 1 to 18 months after the onset of the illness. The EDTA-treated blood specimens were inoculated into ECV304 cells, and cultures were maintained for 7 months. Sequencing of the 56-kDa type-specific antigen gene of O. tsutsugamushi was performed to ascertain the homology of isolates. O. tsutsugamushi was isolated from all six patients, and nucleotide sequences of isolates serially collected from each patient were identical in all five patients in whom nucleotide sequences were compared. One patient relapsed 2 days after completion of antibiotic therapy; two patients complained of weakness for 1 to 2.5 months after the illness; one patient underwent coronary angioplasty 6 months later; and one patient suffered from a transient ischemic attack 8 months later. This finding suggests that O. tsutsugamushi causes chronic latent infection, which may be associated with certain clinical illnesses, preceded by scrub typhus. Antibiotic therapy abates the symptoms of scrub typhus, but does not eradicate O. tsutsugamushi from the human body.
Adult ; Aged ; Aged, 80 and over ; Antigens, Bacterial/genetics ; Bacterial Proteins/genetics ; Base Sequence ; Case-Control Studies ; Chronic Disease ; Coronary Artery Disease/etiology ; DNA, Bacterial/genetics/isolation & purification ; Female ; Genes, Bacterial ; Humans ; Ischemic Attack, Transient/etiology ; Male ; Membrane Proteins/genetics ; Middle Aged ; Muscle Weakness/etiology ; Orientia tsutsugamushi/genetics/immunology/*isolation & purification ; Recurrence ; Scrub Typhus/complications/drug therapy/*microbiology ; Time Factors

PURPOSE: Cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 play a key role in the pathogenesis of in-stent restenosis. We investigated the effect of a short-term therapy of celecoxib, a COX-2 inhibitor, with or without doxycycline, an MMP inhibitor, after coronary stenting on inflammatory biomarkers and neointimal hyperplasia. MATERIALS AND METHODS: A total of 75 patients (86 lesions) treated with bare metal stents were randomized into three groups: 1) combination therapy (200 mg celecoxib and 20 mg doxycycline, both twice daily), 2) celecoxib (200 mg twice daily) only, and 3) non-therapy control. Celecoxib and doxycycline were administered for 3 weeks after coronary stenting. The primary endpoint was neointimal volume obstruction by intravascular ultrasound (IVUS) at 6 months. The secondary endpoints included clinical outcomes, angiographic data, and changes in blood levels of inflammatory biomarkers. RESULTS: Follow-up IVUS revealed no significant difference in the neointimal volume obstruction among the three treatment groups. There was no difference in cardiac deaths, myocardial infarctions, target lesion revascularization or stent thrombosis among the groups. Blood levels of high-sensitivity C-reactive protein, soluble CD40 ligand, and MMP-9 varied widely 48 hours and 3 weeks after coronary stenting, however, they did not show any significant difference among the groups. CONCLUSION: Our study failed to demonstrate any beneficial effects of the short-term therapy with celecoxib and doxycycline or with celecoxib alone in the suppression of inflammatory biomarkers or in the inhibition of neointimal hyperplasia. Large scale randomized trials are necessary to define the role of anti-inflammatory therapy in the inhibition of neointimal hyperplasia.
Aged ; Angioplasty, Balloon, Coronary ; Anti-Bacterial Agents/therapeutic use ; Biological Markers/metabolism ; Coronary Artery Disease/immunology/metabolism/*therapy ; Cyclooxygenase 2 Inhibitors/therapeutic use ; Doxycycline/*therapeutic use ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Humans ; Male ; Metals ; Middle Aged ; Neointima/*drug therapy/*immunology/metabolism ; Pyrazoles/*therapeutic use ; Stents/*adverse effects ; Sulfonamides/*therapeutic use

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

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

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

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

INTRODUCTIONMany studies have reported on the association between human coronary artery disease (CAD) and certain persistent bacterial and viral infections. Currently, it is unclear whether hepatitis B virus infection is associated with the risk of the atherosclerosis. The aim of this study was to investigate the possible association between hepatitis B virus infection and angiography-proven CAD.

MATERIALS AND METHODSSera from 5,004 patients who underwent coronary angiography were tested for hepatitis B surface antigen (HBsAg) by enzyme-linked immunosorbant assay at Madani Heart Hospital, Tabriz University of Medical Sciences, Iran.

RESULTSOur study population comprised 66% male and 34% female, with an age range of 36 to 86 years. The prevalence of HBsAg positivity tended to be higher in CAD patients than in those without CAD (3.28% versus 2.17%), but the difference was not statistically significant.

CONCLUSIONOur results suggest that hepatitis B virus infection is not associated with coronary atherosclerosis in this population.

Child, Preschool ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Cholesterol, VLDL ; blood ; Coronary Angiography ; Coronary Artery Disease ; diagnosis ; epidemiology ; etiology ; Cross-Sectional Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Hepatitis B ; blood ; complications ; epidemiology ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; immunology ; Humans ; Incidence ; Infant ; Iran ; epidemiology ; Male ; Retrospective Studies ; Risk Factors ; Sex Distribution