NLRP3 inflammasome in peripheral blood monocytes of acute coronary syndrome patients and its relationship with statins.

OBJECTIVES: Despite recent advances in the understanding of the role of NLRP3 inflammasomes in coronary atherosclerosis, further work on their activation and clinical implications remains to be performed. In this study, we aimed to evaluate the effect of the dose of rosuvastatin on NLRP3 and cathepsin-B expression in peripheral blood monocytes in patients with acute coronary syndrome. METHODS: A total of 123 participants were enrolled in this study; these included acute myocardial infarction (AMI) patients (n=53), unstable angina patients (UA, n=40), and normal controls (n=30). AMI and UA patients were divided into high-dose rosuvastatin (20 mg) and low-dose rosuvastatin (5 mg) groups. NLRP3, cathepsin-B, and downstream cytokine expressions were appropriately evaluated using real-time PCR, flow cytometry, western blotting and enzyme-linked immunosorbent assay. The concentrations of serum inflammatory markers were also evaluated for correlation with NLRP3 levels. RESULTS: AMI and UA patients had higher NLRP3, cathepsin-B, interleukin-18 (IL-18), pro-IL-18, IL-1ß, and pro-IL-1ß expressions as compared with the control group (P<0.05). This corresponded with higher levels of serum total cholesterol, serum low-density lipoprotein cholesterol, and oxidized low-density lipoprotein in UA and AMI patients (P<0.05). Rosuvastatin at a concentration of 20 mg led to a significant decrease (P<0.05) in the expressions of NLRP3, cathepsin-B, and their downstream cytokines as compared with 5 mg rosuvastatin (P>0.05) from baseline to 4 weeks. This study also showed a positive correlation between NLRP3, cathepsin-B, and downstream inflammatory mediators. CONCLUSION: NLRP3 is involved in inflammation that leads to atherosclerosis. A high dose of rosuvastatin can modulate the inflammatory process of atherosclerosis by downregulating the expression of NLRP3, cathepsin-B, and their downstream mediators. These findings provide insight into the pathogenesis and management of acute coronary syndrome, with NLRP3 as the potential target.

[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.

[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.

Effects of Ginkgo leaf extract on function of dendritic cells and Th1/Th2 cytokines in patients with unstable angina pectoris.

OBJECTIVE: To 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). METHODS: Fifty-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. RESULTS: After 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. CONCLUSION: The 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.

High-dose atorvastatin reduces total plasma levels of oxidized phospholipids and immune complexes present on apolipoprotein B-100 in patients with acute coronary syndromes in the MIRACL trial.

BACKGROUND: Oxidized phospholipids (OxPL) are present within atherosclerotic plaques and bound by lipoprotein (a) [Lp(a)] in plasma. This study evaluated the impact of atorvastatin on oxidized LDL (OxLDL) in patients with acute coronary syndromes (ACS). METHODS AND RESULTS: OxLDL-E06 (OxPL content on apolipoprotein B-100 [apoB] detected by antibody E06), apoB-100 immune complexes (apoB-IC), OxLDL autoantibodies, and Lp(a) levels were measured in 2341 patients at baseline and after 16 weeks of treatment with atorvastatin 80 mg/d or placebo. The OxLDL-E06 and apoB-IC data are reported per apoB-100 particle (OxPL/apoB, IC/apoB) and as total levels on all apoB-100 particles (total apoB-OxPL and total apoB-IC [eg, OxPL/apoB or IC/apoBxapoB-100 levels]). Compared with baseline values, atorvastatin reduced apoB-100 (-33%), total apoB-OxPL (-29.7%), total apoB-IC IgG (-29.5%), and IgM (-25.7%) (P<0.0001 for all), whereas no change or an increase was observed with placebo. When normalized per apoB-100, compared with placebo, atorvastatin increased OxPL/apoB (9.5% versus -3.9%, P<0.0001) and Lp(a) (8.8% versus -0.7%, (P<0.0001). A strong correlation was noted between OxPL/apoB and Lp(a) (R=0.85, P<0.0001), consistent with previous data that Lp(a) binds OxPL. CONCLUSIONS: After atorvastatin treatment, total OxPL on all apoB-100 particles was decreased. However, there was enrichment of OxPL on a smaller pool of apoB-100 particles, in parallel with similar increases in Lp(a), suggesting binding by Lp(a). These data support the hypothesis that atorvastatin promotes mobilization and clearance of proinflammatory OxPL, which may contribute to a reduction in ischemic events after ACS.

High-dose atorvastatin enhances the decline in inflammatory markers in patients with acute coronary syndromes in the MIRACL study.

BACKGROUND: Inflammation promotes acute coronary syndromes and ensuing clinical complications. Although statins reduce inflammatory markers in asymptomatic adults or in patients with stable angina, the effect of statins on the markedly heightened inflammation in patients with acute coronary syndromes is unknown. METHODS AND RESULTS: We measured C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) in 2402 subjects enrolled the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study. Subjects with unstable angina or non-Q-wave myocardial infarction were randomized to atorvastatin 80 mg/d or placebo within 24 to 96 hours of hospital admission and treated for 16 weeks. The effect of treatment on inflammatory markers was assessed by ANCOVA after adjustment for presenting syndrome, country, and initial level of marker. All 3 markers were markedly elevated at randomization and declined over the 16 weeks in both treatment groups. Compared with placebo, atorvastatin significantly reduced CRP, -83% (95% CI, -84%, -81%) versus -74% (95% CI, -75%, -71%) (P<0.0001) and SAA, -80% (95% CI, -82%, -78%) versus -77% (-79%, -75%) (P=0.0006) but not IL-6, -55% (95% CI, -57%, -53%) versus -53% (95% CI, -55%, -51%) (P=0.3). Reductions in CRP and SAA were observed in patients with unstable angina and non-Q-wave myocardial infarction, with initial LDL cholesterol <3.2 or > or =3.2 mmol/L (125 mg/dL), age > or =65 or <65 years, and in men and women. By 16 weeks, CRP was 34% lower with atorvastatin than with placebo. CONCLUSIONS: High-dose atorvastatin potentiated the decline in inflammation in patients with acute coronary syndromes. This supports the value of early statin therapy in these patients.

Psychological factors correlate meaningfully with percent-monocytes among acute coronary syndrome patients.

Recent research demonstrates the importance of inflammatory parameters in the etiology and prognosis of the acute coronary syndrome (ACS). This study explored relations between psychological factors and immunological parameters routinely measured among ACS patients. Forty-two ACS patients completed questionnaires assessing perceived-control, emotional support, hostility, and life-events 2-4 days after hospitalization. Data on total leukocytes and percentages (%) of monocytes, %neutrophils, and %lymphocytes upon admission to hospital were collected from computerized medical charts as well as various biomedical information and risk-factors (e.g., diagnosis, left-ventricle-LV functioning, smoking, and hypertension). Of all significant biomedical variables, LV-function and arrival-time correlated uniquely with total leukocytes. Controlling for LV-function and arrival-time, hostility and life-events positively correlated with %monocytes, and perceived-control and emotional-support inversely correlated with %monocytes. Emotional-support was positively correlated and life-events were negatively correlated with %neutrophils. Macrophages play a pivotal role in plaque instability, the trigger of an ACS. This initiating role, and our finding of a relationship between recruitment of monocytes and a poor psychosocial profile, predictive of ACS, are consistent with a PNI component in the pathophysiology of ACS.