Search

Pure plant extract luteolin has been demonstrated to possess numerous biological effects. However, the specific effect of luteolin on macrophage polarization and NOD-like receptor protein 3 (NLRP3) inflammasome activation has not been documented. In this study, Cultured RAW264.7 cells were treated with or without luteolin in the presence or absence of LPS. Subsequently, cell viability was tested by CCK-8 assay. Total reactive oxygen species (ROS) were measured by flow cytometry. NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), caspase-1, inducible nitric oxide synthase (iNOS) and Arginase (Arg-1) protein expression was detected using western blotting. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect the level of TNF-α, IL-18, and Interleukin-1β (IL-1β). Increased production of ROS and expression of NLRP3, ASC, caspase-1, IL-18 and IL-1β proteins were observed in RAW264.7 cells incubated with LPS and were effectively inhibited by 2 μM luteolin. Furthermore, 2 μM luteolin pretreatment enhanced the expression of M2 macrophage markers (Arg-1 and IL-10), and decreased the expression of markers associated with M1 macrophage polarization (TNF-α, IL-6 and iNOS). These results indicated that low-dose luteolin inhibits NLRP3 inflammasomes activation and promotes macrophage polarization toward an M2 phenotype, which provides new evidence for the anti-inflammation activity of luteolin., Competing Interests: None.

The appropriate assessment of intermediate coronary artery stenosis continues to be a challenge for cardiologists. Several studies have shown that anatomic parameters obtained by intravascular ultrasound (IVUS) and optical coherence tomography (OCT) showed a correlation with fractional flow reserve (FFR) values in identifying hemodynamically severe coronary stenoses. However, the efficacy of IVUS/OCT versus FFR integration in intermediate coronary lesions is still debated. This review will allow for an independent analysis of research data and outlines the diagnostic efficiency of IVUS and OCT derived-anatomical parameters in identifying the hemodynamic significance of an angiographically intermediate stenosis as determined by FFR.

Objective: To investigate the effects of peroxisome proliferator-activated receptor (PPAR) α/γ agonist on atherosclerotic plaque stabilization in diabetic LDL receptor knockout (LDLr-/-) mice., Methods: Female 4-week-old LDLr-/- mice fed with high-glucose and high-fat diet for 4 weeks were randomly divided into three groups (n = 15 each): control group (only fed with high-glucose and high-fat diet), diabetic group [induced by high-glucose and high-fat diet combined with a low-dose of streptozotocin (STZ)] without tesaglitazar and with tesaglitazar (20 µg/kg oral treatment). After 6 weeks, the mice were sacrificed, body weight, fasting blood glucose (Glu), total cholesterol (TC), triglyceride (TG) levels were measured. The expression of ICAM-1, VCAM-1, MCP-1 in the brachiocephalic atherosclerotic lesions were determined by Western blot and immunohistochemistry, respectively. Brachiocephalic artery was prepared for morphologic study (HE, oil red O, Sirius red staining) and immunohistochemical analysis (macrophage surface molecule-3, α-smooth muscle actin), respectively., Results: Serum TC [(32.34 ± 3.26) mmol/L vs. (16.17 ± 1.91) mmol/L], TG [(3.57 ± 0.99) mmol/L vs. (2.21 ± 0.11) mmol/L] and Glu [(15.21 ± 4.67) mmol/L vs. (6.89 ± 0.83) mmol/L] levels were significantly higher in diabetic group than in the control group (all P < 0.01). The expression of ICAM-1 (2.31 ± 0.35 vs.1.34 ± 0.21), VCAM-1 (1.65 ± 0.14 vs.0.82 ± 0.26), MCP-1 (2.27 ± 0.16 vs.1.56 ± 0.23) were significantly upregulated in diabetic group compared with control group (all P < 0.01). Brachiocephalic atherosclerotic plaque area [(4.597 ± 1.260)×10(3) µm(2) vs. (0.075 ± 0.030)×10(3) µm(2)], lipid deposition [(47.23 ± 2.64)% vs. (9.67 ± 1.75)%], Mac-3 positive area [(19.15 ± 3.51)% vs. (1.72 ± 0.16)%], α-smooth muscle actin [(5.54 ± 1.17)% vs. (2.13 ± 0.41)%] and collagen content [(4.27 ± 0.74)% vs. (0.43 ± 0.09)%] were all significantly larger/higher in diabetic LDLr-/- mice than in the control group (all P < 0.01). While tesaglitazar treatment significantly reduced serum TC [(30.47 ± 3.18) mmol/L], TG [(3.14 ± 0.71) mmol/L] and Glu [(7.92 ± 1.28) mmol/L] levels (all P < 0.01). Similarly, the expression of ICAM-1 [(1.84 ± 0.22)], VCAM-1 [(1.27 ± 0.11)], MCP-1 [(1.83 ± 0.24)], brachiocephalic atherosclerotic lesion area[(1.283 ± 0.410)×10(3) µm(2)], lipid deposition[(23.52 ± 1.39)%] were also significantly reduced by tesaglitazar (all P < 0.05). Moreover, tesaglitazar increased α-smooth muscle actin [(9.46 ± 1.47)%] and collagen content [(6.32 ± 1.15)%] in diabetic LDLr-/- mice (all P < 0.05). In addition, lipid deposition and Mac-3 positive areas [(10.67 ± 0.88)% vs. (15.83 ± 1.01)%] in the aortic root were also reduced in tesaglitazar treated diabetic LDLr-/- mice (P < 0.01)., Conclusions: Tesaglitazar has anti-inflammatory effects in the diabetic LDLr-/- mice. Tesaglitazar could reduce lipid deposition, increase collagen and α-SMA content in the brachiocephalic atherosclerotic lesions, thus, stabilize atherosclerotic plaque in this model.

Objective: To evaluate the efficacy and safety of early percutaneous coronary intervention (PCI) within 24 hours of thrombolysis in acute ST-elevation myocardial infarction., Methods: The databases of Medline, EMBASE, Elsevier, Cochrane library, Wanfang and CNKI were searched for randomized controlled trials. Quality assessment and data extraction were performed by two independent reviewers. Statistical analyses were conducted with Stata 10.0 and RevMan 5.0 software., Results: Eight studies (NORDI-STEMI, TRANSFER-AMI, WEST, CARESS-AMI, CAPITAL-AMI, GRACIA-I, SIAMI III & PRAGUE-I) involving a total of 3157 patients fulfilled the inclusion criteria. Meta-analysis results showed that, as compared with the control group, (1) the combined endpoint of 30 day mortality, re-infarction and ischemia was significantly lower in early PCI within 24 h of thrombolysis group [relative risk (RR) = 0.52, 95% confidence interval (CI) 0.42 - 0.65, P < 0.001]; (2) 30-day re-infarction decreased in early PCI within 24 h of thrombolysis group (RR = 0.57, 95%CI 0.40 - 0.81, P = 0.002); (3) 30-day ischemia had a significant reduction in early PCI within 24 h of thrombolysis group (RR = 0.27, 95%CI 0.14 - 0.52, P < 0.001); (4) 30-day major hemorrhage or mortality rates were not significantly different between two groups (RR = 1.07, 95%CI 0.78-1.46, P = 0.69; RR = 0.86, 95%CI 0.62 - 1.20, P = 0.38 respectively)., Conclusion: When primary PCI is not feasible, our meta-analysis favors early PCI within 24 h of thrombolysis for acute ST-elevation myocardial infarction. Early PCI is associated with a lowered recurrence of major adverse cardiac events, ischemia and re-infarction. But there is no elevated risk of major hemorrhage and mortality.