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Purpose: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is involved in the pathogenesis of atherosclerosis, especially in advanced plaques. In the present study, the abilities of darapladib, a selective Lp-PLA2inhibitor, and lentivirus-mediated Lp-PLA2 silencing on inflammation and atherosclerosis in apolipoprotein E-defficient mice were compared. Methods: Apolipoprotein E-deficient mice were fed on a high-fat diet and a constrictive collar was placed around the left carotid artery to induce plaque formation. The mice were randomly divided into control, negative control (NC), darapladib and RNA interference (RNAi) groups. Eight weeks after surgery, lentivirus-mediated RNAi construct or darapladib were used to decrease the expression of Lp-PLA2. Plaques were collected ve weeks later for histological analysis. Inflammatory gene expression in the atherosclerotic lesions were then determined at the mRNA and protein level. Results: The expression of pro-inflammatory cytokines was significantly reduced in the treatment group, compared to nontreatment group, whereas the plasma concentration of anti-inflammatory cytokines increased markedly. Moreover, our results demonstrated a signifcant reduction in plaque lipid content, as well as a rise in collagen content following Lp-PLA2 inhibition. Interestingly, when comparing the two methods of Lp-PLA2 inhibition, animals treated with Lp-PLA2 RNAi were found to exhibit lower plaque areas and enhanced improvement of plaque stability as compared with animals treated with darapladib. Darapladib had no attenuating effect on atherosclerotic plaque area. These therapeutic effects were independent of plasma lipoprotein levels. Conclusions: Lp-PLA2 inhibition by darapladib or lentivirus-mediated RNAi ameliorated inflammation and atherosclerosis in apolipoprotein E-defficient mice. The effect was more prominent in the RNAi group. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the levels of pregnancy-associated plasma protein A (PAPP-A) or insulin-like growth factor -1 (IGF-1) in patients with acute coronary syndrome. Methods: Serum PAPP-A and IGF-1 was measured with biotin-tyramide-amplified enzyme immunoassay and Enzyme Linked Immuoserbent Assay, respectively, in patients with ST elevation acute myocardial infarction (STEMI, n=12), unstable angina (UAP, n=15), and stable angina (n=15). PAPP-A and IGF-1 was also measured in 16 healthy subjects (control group). Results: The serum levels of PAPP-A in the STEMI (16.9±10.3 mIU/L) and UAP group (15.2±10.5 mIU/L) were higher than in the stable angina (8.5±3.1 mIU/L) or control group (8.4±2.0 mIU/L, P<0.01). The serum levels of IGF-1 in the STEMI (132.3±40.9 μg/L) and UAP group (127.3±36.0 μg/L) were also higher than in the stable angina (44.9±18.5 μg/L) or control group (67.7±24.5 μg/L, P<0.01). There were no differences in serum levels of PAPP-A or IGF-1 among the single, double and three vessel lesion groups. The serum levels of PAPP-A (19.9±10.1 mIU/L) and IGF-1 (153.2±52.4 μg/L) after PCI were higher than those before PCI (15.1±10.0 mIU/L and 91.4±51.0 μg/L, respectively, P<0.01). A positive correlation was found between PAPP-A and IGF-1 levels in the STEMI and UAP group before PCI (r=0.48,P<0.01). Conclusion: PAPP-A and IGF-1 are elevated in patients with acute coronary syndrome. They may be used as biomarkers for vulnerable plaques in patients with coronary artery disease. Whether post-PCI elevation of IGF-1 can be used to predict restenosis of coronary arteries remains to be seen. [ABSTRACT FROM AUTHOR]

Purpose: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is involved in the pathogenesis of atherosclerosis, especially in advanced plaques. In the present study, the abilities of darapladib, a selective Lp-PLA(2) inhibitor, and lentivirus-mediated Lp-PLA(2) silencing on inflammation and atherosclerosis in apolipoprotein E-deficient mice were compared.Methods: Apolipoprotein E-deficient mice were fed on a high-fat diet and a constrictive collar was placed around the left carotid artery to induce plaque formation. The mice were randomly divided into control, negative control (NC), darapladib and RNA interference (RNAi) groups. Eight weeks after surgery, lentivirus-mediated RNAi construct or darapladib were used to decrease the expression of Lp-PLA(2). Plaques were collected five weeks later for histological analysis. Inflammatory gene expression in the atherosclerotic lesions were then determined at the mRNA and protein level.Results: The expression of pro-inflammatory cytokines was significantly reduced in the treatment group, compared to nontreatment group, whereas the plasma concentration of anti-inflammatory cytokines increased markedly. Moreover, our results demonstrated a significant reduction in plaque lipid content, as well as a rise in collagen content following Lp-PLA(2) inhibition. Interestingly, when comparing the two methods of Lp-PLA(2) inhibition, animals treated with Lp-PLA(2) RNAi were found to exhibit lower plaque areas and enhanced improvement of plaque stability as compared with animals treated with darapladib. Darapladib had no attenuating effect on atherosclerotic plaque area. These therapeutic effects were independent of plasma lipoprotein levels.Conclusions: Lp-PLA(2) inhibition by darapladib or lentivirus-mediated RNAi ameliorated inflammation and atherosclerosis in apolipoprotein E-deficient mice. The effect was more prominent in the RNAi group. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the levels of interleukin-33 (IL-33) and interleukin-6 (IL-6) in patients with acute coronary syndrome or stable angina. Methods: Serum IL-33 and IL-6 were measured with Enzyme Linked Immuosorbent Assay (ELISA) in patients with acute coronary syndrome (ACS, n = 40), and stable angina pectoris (SAP, n = 43). IL-33 and IL-6 were also determined in 30 healthy subjects (control group). Results: The serum level of IL-33 in the ACS group (78.60 ± 44.84 ng/L) was lower than in the SAP (102.58 ± 37.21 ng/L, P<0.01) or control groups (130.24 ± 10.17 ng/L, P<0.01). e serum level of IL-6 in the ACS group (39.90 ± 12.64 ng/L) was higher than in the SAP (18.68 ± 11.89 ng/L, P<0.05) or control groups (6.28 ± 17.72 ng/L, P<0.05). were were no differences in serum levels of IL-33 and IL-6 among the single-, double- and triple-vessel lesion groups. IL-33 and IL-6 levels were negatively correlated with each other in the ACS (r = -0.871, P<0.01) and SAP groups (r = -0.788, P<0.01). Conclusion: The serum level of IL-33 was lower in patients with ACS or SAP and was negatively correlated with the serum level of IL-6. Thus, IL-33 and IL-6 may be used as biomarkers for evaluating inflammatory response and severity of coronary heart disease in patients with ACS or SAP. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the levels of interleukin-33 (IL-33) and interleukin-6 (IL-6) in patients with acute coronary syndrome or stable angina.Methods: Serum IL-33 and IL-6 were measured with Enzyme Linked Immuosorbent Assay (ELISA) in patients with acute coronary syndrome (ACS, n=40), and stable angina pectoris (SAP, n=43). IL-33 and IL-6 were also determined in 30 healthy subjects (control group).Results: The serum level of IL-33 in the ACS group (78.60±44.84 ng/L) was lower than in the SAP (102.58±37.21 ng/L, P<0.01) or control groups (130.24±10.17 ng/L, P<0.01). The serum level of IL-6 in the ACS group (39.90±12.64 ng/L) was higher than in the SAP (18.68±11.89 ng/L, P<0.05) or control groups (6.28±17.72 ng/L, P<0.05). There were no differences in serum levels of IL-33 and IL-6 among the single-, double- and triple-vessel lesion groups. IL-33 and IL-6 levels were negatively correlated with each other in the ACS (r=-0.871, P<0.01) and SAP groups (r=-0.788, P<0.01).Conclusion: The serum level of IL-33 was lower in patients with ACS or SAP and was negatively correlated with the serum level of IL-6. Thus, IL-33 and IL-6 may be used as biomarkers for evaluating inflammatory response and severity of coronary heart disease in patients with ACS or SAP. [ABSTRACT FROM AUTHOR]