Comprehensive analysis of T-cell receptor repertoire in patients with acute coronary syndrome by high-throughput sequencing.

BACKGROUND: This study aims to investigate the T-cell receptor (TCR) repertoire in patients with acute coronary syndrome (ACS). METHODS: The TCR repertoires of 9 unstable angina patients (UA), 14 acute myocardial infarction patients (AMI) and 9 normal coronary artery (NCA) patients were profiled using high-throughput sequencing (HTS). The clonal diversity of the TCR repertoires in different groups was analyzed, as well as the frequencies of variable (V), diversity (D) and joining(J) gene segments. RESULTS: ACS patients including UA and AMI, showed reduced TCRß diversity than NCA patients. ACS patients presented higher levels of clonal expansion. The clonotype overlap of complementarity determining region 3(CDR3) was significantly varied between different groups. A total of 10 V genes and 1 J gene were differently utilized between ACS and NCA patients. We identified some shared CDR3 amino acid sequences that were presented in ACS but not in NCA patients. CONCLUSIONS: This study revealed the distinct TCR repertoires in patients with ACS and demonstrated the presence of disease associated T-cell clonotypes. These findings suggested a role of T cells in ACS and provided a new way to explore the mechanisms of ACS.

Cytokine expression profile and blood parameter evaluation of patients undergoing cardiac surgery.

Cardiac surgery is accompanied by an important immune response that is poorly understood. This inflammatory response is caused by several stimuli: surgical trauma, cardiopulmonary bypass apparatus, aortic-cross clamping, reperfusion injury and hypothermia. The aim of the present study is to investigate the cytokine level profile involved in the inflammatory pathway of patients undergoing cardiac surgery. One hundred and two patients undergoing elective cardiac surgery utilizing cardiopulmonary bypass (CPB) apparatus were enrolled in the study. In the hematological and biochemical profiles investigated, we observed a significant increase of WBC and blood glucose concentration and a strong decrease of RBC, HB, HCT and PLT 24 h post-surgery compared to baseline and immediately after surgery groups. Furthermore, we found a modulation of cytokine levels mostly for IL-10 and an increase of IL-6, detected at 6 h post-surgery, IL-8 at 6 and 24 h, and TNFα only at 24 h post-surgery. In conclusion, these findings evidence a time course profile on cytokine levels and a balance between pro- and anti-inflammatory cytokine activation during and after cardiac surgery. In fact, IL-6 and IL-10, a pro- and an anti-inflammatory cytokine, respectively, increased immediately after surgery. The plasma level of TNF-α could be inhibited by the high concentration of IL-10 up to 6 h post-surgery. An IL-10 reduction at baseline level, after 24 h post-surgery, could explain a rise of TNF-α plasma concentration. On the other hand, considering the dual role of IL-6 on inflammation acting both as an activator of inflammatory cascade or an anti-inflammatory agent, the increased IL-6 levels 24 h after surgery could be related to the negative feedback action on TNFα activity.

A decrease in the percentage of circulating mDC precursors in patients with coronary heart disease: a relation to the severity and extent of coronary artery lesions?

Inflammation plays a pivotal role in coronary heart disease. Dendritic cells (DCs) are principal players in inflammation and atherosclerosis. Although the percentage of circulating DC precursors in coronary heart disease have been investigated, circulating myeloid DC (mDC) and plasmacytoid DC (pDC) precursors have not been extensively studied, particularly in relation to the severity of coronary artery lesions in patients with coronary heart disease. In this study, we recruited controls (n = 29), patients with stable angina pectoris (SAP, n = 30), patients with unstable angina pectoris (UAP, n = 56), and patients with acute myocardial infarction (AMI, n = 50). The severity and extent of coronary artery lesions was evaluated by Gensini score, following coronary angiograms. The percentage of circulating mDC and pDC precursors was determined by fluorescence-activated cell sorting (FACS). Plasma levels of MCP-1 and MMP-9, which correlate with atherosclerosis and DC migration, were also measured. The percentage of circulating mDC precursors was reduced in patients with AMI and UAP compared with control and SAP patients, respectively (p < 0.01 for AMI vs. SAP and Control, p < 0.05 for UAP vs. SAP and Control). The percentage of circulating pDC precursors was not significant changed. The levels of plasma MMP-9 and MCP-1 and Genisi score were all increased in patients with AMI and UAP, compared to control and SAP patients, respectively (p < 0.01 for AMI vs. SAP and control, p < 0.05 for UAP vs. SAP and control). Overall, the percentage of circulating mDC precursors was negatively correlated with MCP-1 (p < 0.001), MMP-9 (p < 0.001) and Genisi scores (p < 0.001). Genisi scores were positively correlated with the levels of MCP-1 (p < 0.001) and MMP-9 (p < 0.001). Our study suggested that the percentage of circulating mDC precursors is negatively correlated with the severity and extent of coronary artery lesions in patients with coronary heart disease.

Galectin-3 plasma levels and coronary artery disease: a new possible biomarker of acute coronary syndrome.

Inflammation plays a key role in atherosclerosis. Galectin-3 is a macrophage- and endothelium-derived mediator actively involved in the regulation of many aspects of inflammatory cell behaviour. The aim of this study is to quantify plasma Galectin-3 in patients with coronary artery disease (CAD) and different clinical manifestation at the moment of observation in order to verify whether Galectin-3 could be a useful biomarker of atherosclerotic state. We enrolled 125 patients affected by CAD, angiographically documented (70 stable, 55 unstable). They underwent accurate examinations and anamnestic data was collected. The most important traditional risk factors, such as age, hypertension, and body mass index, were reported. Plasma Galectin-3 was quantified using an ELISA kit. Unstable patients (n = 55) had a higher plasma Galectin-3 levels in respect to the stable subjects (27.75 ng/mL (19.27-39.09) vs 6.48 ng/ml (4.88-8.83), p<0.001. A trend in correlation between plasma Galectin-3 levels and number of vessels compromised seems to be present: CAD patients with three-vessel disease had higher levels of Galectin-3 than patients with one-or two-vessel disease (17.39 ng/ml (10.75-29.82) vs 9.18 ng/ml (5.56-23.22), p= 0.058. The significantly higher plasma Galectin-3 levels in patients with unstable angina in respect to the stable angina confirm the involvement of Galectin-3 in promoting macrophage activation and monocyte attraction. Despite the distribution of CAD in patients with acute and chronic coronary disease being similar, we may hypothesize that Galectin-3 could be a useful biomarker of atherosclerotic plaque and in particular of its destabilization.

Trace element, immune and opioid biomarkers of unstable angina, increased atherogenicity and insulin resistance: Results of machine learning.

BACKGROUND: Aberrations in endothelial cells, immune and oxidative pathways are associated with atherosclerosis (ATS) and unstable angina (UA). The role of trace elements, minerals, and the endogenous opioid system (EOS) in UA are less well established. METHODS: We measured lipid, insulin resistance (IR), and immune, trace element (copper and zinc), mineral (magnesium, calcium), EOS (ß-endorphin and mu-opioid receptor (MOR)) and antioxidant (vitamin D3) biomarkers in patients with ATS (n = 60) and UA (n = 60) and healthy controls (n = 58). RESULTS: ATS patients showed increased atherogenic and IR indices, IL-6, IL-10, ß-endorphin, copper and magnesium, and lower zinc than healthy controls. Logistic regression showed that UA was significantly discriminated from ATS without UA with an accuracy of 85.5 % using calcium, IL-10, ß-endorphin, MOR, triglycerides, IR (all positively), and copper and vitamin D3 (inversely). Neural networks showed that UA was discriminated from ATS without UA with an area under the ROC curve of 0.942 using MOR, ß-endorphin, calcium, insulin resistance, vitamin D3 and copper as input variables. We found that 50.0 % of the variance in IR was explained by the regression on copper, IL-10, IL-6 (all positively), and zinc (inversely), while 32.9 % of the variance in the atherogenic index of plasma was explained by copper, IL-10 (both positively), and magnesium (inversely). CONCLUSION: UA is not only mediated by insulin resistance, atherogenicity, and immune disorders, but also by aberrations in the endogenous opioid system and trace elements as well as lowered antioxidant levels. Copper appears to play a key role in IR and atherogenicity.

Activated endocannabinoid system in coronary artery disease and antiinflammatory effects of cannabinoid 1 receptor blockade on macrophages.

BACKGROUND: Cannabinoid 1 (CB1) receptor blockade with rimonabant represents a clinical therapeutic strategy for obesity. Recently, the role of the endocannabinoid system has been described in peripheral organs. We sought to determine whether the endocannabinoid system could be involved in human atherosclerosis and whether CB1 receptor blockade could modulate proinflammatory activity in macrophages. METHODS AND RESULTS: mRNA expression levels of CB1 receptor in coronary atherectomy samples were significantly higher in patients with unstable angina than in those with stable angina (3.62+/-2.96-fold; n=7; P<0.05). Immunoreactive area analysis of the coronary artery showed that CB1 receptor expression was greater in lipid-rich atheromatous plaques than in fibrous plaques, especially in CD68 macrophages (9.5+/-1.2% versus 0.6+/-0.6%; n=5; P<0.01). Levels of blood endocannabinoids were significantly higher in patients with coronary artery disease (n=20) than those without coronary artery disease (n=20) (median [interquartile range]: anandamide, 1.048 pmol/mL [0.687 to 1.387 pmol/mL] versus 0.537 pmol/mL [0.468 to 0.857 pmol/mL], P<0.01; 2-arachidonoyl glycerol, 13.30 pmol/mL [6.65 to 16.21 pmol/mL] versus 7.67 pmol/mL [6.39 to 10.03 pmol/mL], P<0.05). In cultured macrophages, expression of CB1 receptor was significantly increased during monocyte-macrophage differentiation (1.78+/-0.13-fold; n=6; P<0.01). CB1 receptor blockade in macrophages induced a significant increase in cytosolic cAMP (29.9+/-13.0%; n=4; P<0.01), inhibited phosphorylation of c-Jun N-terminal kinase (-19.1+/-12.6%, n=4; P<0.05), and resulted in a significant decrease in the production of proinflammatory mediators (interleukin-1beta, -28.9+/-10.9%; interleukin-6, -24.8+/-7.6%; interleukin-8, -22.7+/-5.2%; tumor necrosis factor-alpha, -13.6+/-4.8%; matrix metalloproteinase-9, -16.4+/-3.8%; n=4 to 8; P<0.01). CONCLUSIONS: Patients with coronary artery disease demonstrated the activation of the endocannabinoid system with elevated levels of blood endocannabinoids and increased expression of CB1 receptor in coronary atheroma. CB1 receptor blockade exhibited antiinflammatory effects on macrophages, which might provide beneficial effects on atherogenesis.

Upregulation of fractalkine and its receptor, CX3CR1, is associated with coronary plaque rupture in patients with unstable angina pectoris.

BACKGROUND: Recent studies suggest that fractalkine (FKN or CX3CL1) and its cognate receptor, CX3CR1, play a role in atherogenesis, so the relationship between coronary plaque rupture, as observed by preintervention optical coherence tomography, and plasma levels of FKN and CX3CR1 was investigated in this study. METHODS AND RESULTS: The study population consisted of 46 patients with unstable angina pectoris (UAP), 30 patients with stable angina pectoris, and 25 healthy controls. The UAP patients underwent a preintervention optical coherence tomography study, which revealed that the number of patients with and without plaque rupture at the culprit site was 27 (rupture group) and 19 (non-rupture group), respectively. Plasma levels of soluble FKN (sFKN) and CX3CR1 were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively. The plasma levels of sFKN were significantly increased in UAP patients with plaque rupture compared with patients in the other groups. Multiple logistic regression analysis showed that CD14(+)CD16(+)CX3CR1(+) monocytes and CD3(+)CX3CR1(+) lymphocytes were independent predictors of the presence of ruptured plaque. CONCLUSIONS: Increases in the FKN level and the number of CX3CR1-expressing mononuclear cells might contribute to coronary plaque rupture.

Circulating soluble CD40 ligand mediates the interaction between neutrophils and platelets in acute coronary syndrome.

Following plaque rupture, activated platelet will induce subsequent inflammatory process including neutrophil recruitment. In vitro study demonstrated an interaction between neutrophils and platelets via a mechanism involving CD40-CD40 ligand. However, whether this mechanism exists in the clinical setting remains unknown. Fifty-four patients with acute myocardial infarction (AMI) and 25 with unstable angina of pain onset of < or = 24 h were enrolled consecutively. Acute myocardial infarction was diagnosed from three diagnostic criteria, i.e., anginal pain, electrocardiogram ST-T changes, and cardiac enzyme elevation. Unstable angina was diagnosed in patients without elevated cardiac enzymes. Peripheral venous blood was drawn at admission for routine blood count and soluble CD40 ligand (sCD40L) measurement. Neutrophil count was determined by an automated blood cell counter. Circulating sCD40L was measured using a standard enzyme-linked immunosorbent assay. Neutrophil count was significantly higher in AMI as compared with unstable angina (P < 0.001), whereas circulating sCD40L did not significantly differ. Despite marked elevation, no correlation was observed between neutrophil count and circulating sCD40L in AMI. Interestingly, we observed a strong and positive significant correlation between neutrophil count and circulating sCD40L level (r = 0.607, P = 0.002) in unstable angina. Circulating sCD40L is associated with neutrophil count and may mediate interaction between neutrophils and platelets in acute coronary syndrome, particularly in unstable angina.

[Immunoglobulins of blood serum in patients with stable and unstable angina].

Article is devoted to the study of immunoglobulins (Ig) classes A, G and M in blood serum of patients with stable and unstable clinical course of ischemic heart disease that improve our knowledge about immuneinflammatory process which develops under destabilization of a coronary circulation.

Serum complement C1q level is associated with acute coronary syndrome.

BACKGROUND AND OBJECTIVES: The complement system plays an important role in the development of acute coronary syndrome (ACS). Complement C1q is an important initial component of the classical complement pathway and closely related to many chronic inflammatory diseases, including atherosclerosis (AS). We aimed to determine whether there was association between serum complement C1q and the severity of coronary stenosis. SUBJECTS AND METHODS: 320 patients who underwent coronary arteriography (CAG) were stratified into non-ACS group (control group, n = 74), unstable angina group (UA group, n = 197) and acute myocardial infarction group (AMI group, n = 49) according to the severity of coronary stenosis and clinical manifestations. The severity of coronary stenosis was represented in Gensini score, and serum complement C1q level was compared using immunity transmission turbidity among three groups. RESULTS: The level of complement C1q in AMI group was lower significantly than control group and UA group (P < 0.05), but there was no correlation between serum complement C1q and Gensini score (ß=-0.086, P = 0.125). In nitrate-taking patients, serum complement C1q had a negative association with Gensini score (r=-0.275, P = 0.001), and in non-smokers, there was also a negative correlation (ß=-0.159, P = 0.036). After calibrating smoking, drinking or statins, the serum complement C1q levels of control group, UA group and AMI group decreased in sequence (P <  0.05). Logistic regression analysis showed that the decreasing of serum complement C1q was an unfavorable factor for acute myocardial infarction (OR=0.984, 95 %CI=0.972∼0.997, P = 0.015) and for ACS (OR=0.984, 95 %CI=0.971∼0.984, P = 0.025) in drinking patients. Regrettably, ROC curve suggested that the accuracy in diagnosing coronary atherosclerotic heart disease by serum complement C1q was low (AUC=0.568, 95 %CI= 0.492-0.644, P = 0.076, sensitivity 73.6 %, specificity 58.1 %). CONCLUSION: Serum complement C1q in ACS patients, in particular AMI patients, showed lower level. This finding suggests further decrease of complement C1q level in ACS patients may be a contributory factor to instability or rupture of atherosclerotic plaques. Combined with other clinical indicators, it can be helpful to predict the risk and severity of coronary stenosis.

Association Between Early Severe Cardiovascular Events and the Initiation of Treatment With the Anti-Interleukin 12/23p40 Antibody Ustekinumab.

Importance: Ustekinumab, a monoclonal antibody targeting interleukin 12/23p40 (IL-12/23p40), is effective in the treatment of moderate to severe psoriasis, psoriatic arthritis, and Crohn disease. In 2011, a meta-analysis of randomized clinical trials reported a potential risk of severe cardiovascular events (SCEs) within the first few months after the initiation of anti-IL-12/23p40 antibodies. Objective: To assess whether the initiation of ustekinumab treatment is associated with increased risk of SCEs. Design, Setting, and Participants: This case-time-control study used data from the French national health insurance database, covering 66 million individuals, on all patients exposed to ustekinumab between April 1, 2010, and December 31, 2016, classified according to their cardiovascular risk level (high- and low-risk strata). The risk period was the 6 months before the SCE, defined as acute coronary syndrome or stroke, and the reference period was the 6 months before the risk period. Statistical analysis was performed from September 20, 2017, to July 6, 2018. Exposure: The initiation of ustekinumab treatment was screened during the risk and reference periods. Main Outcomes and Measures: Odds ratios for the risk of SCE after the initiation of ustekinumab treatment were calculated. Results: Of the 9290 patients exposed to ustekinumab (4847 men [52%]; mean [SD] age, 43 [14] years), 179 experienced SCEs (65 cases of acute coronary syndrome, 68 cases of unstable angina, and 46 cases of stroke). Among patients with a high cardiovascular risk, a statisically significant association between initiaton of ustekinumab treatment and SCE occurrence was identified (odds ratio, 4.17; 95% CI, 1.19-14.59). Conversely, no statistically significant association was found among patients with a low cardiovascular risk (odds ratio, 0.30; 95% CI, 0.03-3.13). Conclusions and Relevance: This study suggests that the initiation of ustekinumab treatment may trigger SCEs among patients at high cardiovascular risk. In line with the current mechanistic models for atherosclerotic disease, the period after the initiation of anti-IL-12/23p40 may be associated with atherosclerotic plaque destabilization via the inhibition of helper T cell subtype 17. Although the study interpretation is limited by its observational design, these results suggest that caution may be needed in the prescription of ustekinumab to patients at high cardiovascular risk.

Beta2-integrin activation on T cell subsets is an independent prognostic factor in unstable angina pectoris.

BACKGROUND: Cardiac troponins provide excellent risk stratification in unstable angina (UA), but no reliable markers are available in troponin-negative patients. Beta2-integrin mediated T cell recruitment plays a pivotal role in coronary atherosclerotic plaque rupture. The present study investigates beta2-integrin activation on T cell subsets as a risk marker in UA. METHODS: Functional activation (affinity/avidity) of beta2-integrins on T cells was measured using a flow cytometry-based whole blood assay in 87 patients with UA. RESULTS: Beta2-integrin activation was significantly higher in patients with severe coronary artery disease (sC) and myocardial infarction (MI) compared to patients with no/minimal coronary atherosclerosis (no/mC), irrespective of troponin status. Adjusted for cardiovascular risk factors, medication, left ventricular function, MI at enrollment and high sensitivity C-reactive protein (hsCRP), beta2-integrin activation was independently associated with incidence of revascularization, hospitalization and all major cardiovascular events during 9 months of follow-up after index investigation. The highest prognostic value of beta2-integrin activation was seen in troponin-and hsCRP-negative patients. CONCLUSION: Quantitative assessment of T cell beta2-integrin activation allows to identify high risk patients with UA and sC without established MI; furthermore, it is associated with incidence of future cardiovascular events independent of conventional risk factors (troponin, hsCRP).

Dendritic cell activation is blunted in patients with coronary artery disease and diabetes mellitus.

BACKGROUND: It has been shown that functional status of dendritic cells (DCs) in diabetic patients with unstable angina pectoris (UAP) are more mature and activated than diabetic patients without coronary artery disease (CAD) and none diabetic patients with UAP. Accordingly we aimed to assess the activation of DCs in patients with CAD with/and without Diabetes Mellitus (DM) and compare to those in subjects with normal coronary arteries (NCA). MATERIALS AND METHODS: Twenty three patients with severe CAD who were scheduled to coronary artery by-pass grafting surgery and 6 patients with angiographycally NCAs were included in the study. Activation of peripheral blood DCs have been analyzed by flow cytometric measures of CD86 activation. RESULTS: In patients with CAD and without DM, DC activation significantly increased after stimulation of oxidesized LDL (135 ±â€¯121 vs 248 ±â€¯197 p = 0.024). However this activation didn't significantly increased in patients with CAD and DM (100 ±â€¯20 vs 120 ±â€¯97, p = 0,54). Patients with NCAs and without DM showed marked activation of CD86 after stimulation with ox-LDL. CONCLUSION: We have documented that DC activation, upon stimulation of ox-LDL has blunted in patients with CAD compared to patients with NCAs. Moreover this defective activation is more pronounced in those with diabetic patients with CAD.

Loss of Regulatory Immune Function in Coronary Artery Disease Patients from the Indian Population.

The pathogenic roles of inflammatory T cells and monocytes subsets have not been explored in different manifestations of coronary artery disease. We studied the frequency of these cells, their response to autoantigens, regulatory cell functional assay, foam cell formation and macrophage differentiation in 181 patients (stable angina, ST-elevated myocardial infarction (STEMI), NSTEMI, and unstable angina), and 34 controls and in samples collected during recurrent cardiac events and from patients showing clinical improvement. The proportion of Th17 cells and monocytes gradually increased in patients with stable angina at one end of the spectrum followed by NSTEMI, STEMI, and unstable angina at other end. Inflammatory cells were positively and inversely associated with recurrent events and clinical improvement, respectively. Patients showed expansion of Th17 cells in response to autoantigen (HSP60) and compromised Treg function. Our results suggest that stress-induced activation of inflammatory cells expands in the absence of regulatory control in CAD patients.

Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis: possible role in inflammation and plaque destabilization.

BACKGROUND: Although the participation of inflammation in atherogenesis is widely recognized, the identification of the different components has not been clarified. In particular, the role of inflammation in plaque destabilization is not fully understood. METHODS AND RESULTS: Our main findings were as follows: (1) In a microarray experiment, we identified visfatin, one of the most recently identified adipokines, as a gene that was markedly enhanced in carotid plaques from symptomatic compared with plaques from asymptomatic individuals. This finding was confirmed when carotid plaques from 7 patients with asymptomatic and 14 patients with symptomatic lesions were examined with real-time reverse transcription polymerase chain reaction. (2) Immunohistochemistry showed that visfatin was localized in areas that were rich in lipid-loaded macrophages. (3) The relationship between visfatin and unstable lesions was also found in patients with coronary artery disease, demonstrating a strong visfatin immunostaining in lipid-rich regions within the material obtained at the site of plaque rupture in patients with acute myocardial infarction. (4) Both oxidized low-density lipoprotein and tumor necrosis factor-alpha increased visfatin expression in THP-1 monocytes, with a particularly enhancing effect when these stimuli were combined. (5) Visfatin increased matrix metalloproteinase-9 activity in THP-1 monocytes and tumor necrosis factor-alpha and interleukin-8 levels in peripheral blood mononuclear cells. Both of these effects were abolished when insulin receptor signaling was blocked. CONCLUSIONS: Our findings suggest that visfatin should be regarded as an inflammatory mediator, localized to foam cell macrophages within unstable atherosclerotic lesions, that potentially plays a role in plaque destabilization.

Antibody titres to heat shock protein 27 are elevated in patients with acute coronary syndrome.

IgG antibody titres to heat shock protein 27 (anti-Hsp27) were measured to determine whether these titres were affected in patients admitted with acute coronary syndrome. Blood samples were taken from 94 patients admitted with acute coronary syndrome. Anti-Hsp27 IgG titres were determined using an in-house enzyme-linked immunosorbent assay (ELISA) in the first and second 12 h after the onset of symptoms and compared with values for 81 age- and sex-matched control subjects. Median antibody titres to Hsp27 in the first sample from patients whose diagnosis was a myocardial infarction (n = 42) was 0.41 absorbancy units (range 0.28-0.57) and for those with unstable angina (n = 52) was 0.31 (range 0.20-0.42), both being significantly higher than for controls (n = 81), which was 0.08 (range 0.05-0.15) (P < 0.05). However, titres fell in the second samples collected in the coronary syndrome patients and were then no longer significantly different from controls (P > 0.05). Myocardial infarction patients also had significantly higher anti-Hsp27 titres in the first 12 h than patients with unstable angina (P < 0.05), but again the difference in the second sample did not reach statistical significance (P > 0.05). Serum antibody titres to Hsp27 rise and fall rapidly after the onset of acute coronary syndrome, and may be an early marker of myocardial ischaemia as patients with myocardial infarction or unstable angina both had high titres.

Autoantibody response to chromatographic fractions from oxidized LDL in unstable angina patients and healthy controls.

Levels of autoantibodies to oxidized low-density lipoprotein (oxLDL) have been correlated to atherosclerosis; however, contradictory results have been shown. To better understand the role of autoantibodies to oxLDL in atherogenesis, and their potential to predict risk of developing coronary artery disease we investigated the antibody response of unstable angina (UA) patients and healthy controls against chromatographic separated fractions of oxLDL. Five major peaks were detected after chromatographic separation of oxLDL and 10 fractions were collected. Surprisingly, when the response to high molecular weight fractions was analysed, we observed a significant increase in the levels of autoantibodies in controls compared to UA. In contrast, when the autoantibody response to intermediate and low molecular weight fractions was analysed, we observed that the UA group showed consistently higher levels compared with controls. Our data demonstrates that within oxLDL there are major fractions that can be recognized by autoantibodies from either UA patients or healthy individuals, and that the use of total oxLDL as an antigen pool may mask the presence of some antigenic molecules and their corresponding antibodies. Further studies are needed, but the analysis of antibody profiles may indeed open up a novel approach for evaluation and prevention against atherosclerosis.

[Effect of compound paeonol dripping pill on levels of plasma inflammatory mediators in patients with unstable angina].

OBJECTIVE: To 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). METHODS: Ninety 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. RESULTS: The 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). CONCLUSION: Effect 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.

[Peripheral dendritic cell subpopulation changes in patients with coronary artery disease].

OBJECTIVE: To compare the peripheral dendritic cell subpopulation changes in patients with or without coronary artery disease. METHODS: A total of 60 patients with angiographic documented coronary artery disease (CAD) were recruited in this study, including 20 cases with acute myocardial infarction (AMI group), 20 cases with unstable angina(UA group) and 20 patients with stable angina (SA group). Eleven patients with chest pain and without coronary stenosis served as chest pain control (CPS group). Ten cases without heart diseases served as normal control (Normal control group). Numbers of peripheral myeloid dendritic cell (mDC) and plasmacytoid dendritic cell (pDC) precursors were determined by FACS. RESULT: The proportions of mDC precursors were significantly lower in UA group and AMI group (4.7% +/- 2.6%, 5.0% +/- 2.7%) than that in SA, CPS and control groups (11.0% +/- 6.4%, 12.0% +/- 3.9%, 12.3% +/- 3.3%, respectively, all P < 0.001). pDC numbers were similar among groups. CONCLUSION: Reduced circulating mDC subsets in patients with unstable angina and AMI might suggest enhanced mDC recruitment to vulnerable plaques in these patients.

[Study on effect of promoting blood circulation drugs components in treating unstable angina in patients with blood stasis inflammatory levels].

OBJECTIVE: To 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). METHOD: one 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. RESULT: Component 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). CONCLUSION: Huoxue-effective component compatibility can be effective treatment of unstable angina blood stasis, and could inhibit the inflammatory level.