Figure 1.
Darapladib significantly inhibits serum lp-PLA2 activity in ApoE-deficient mice.
(A). Five apoE-deficient mice were administrated with darapladib (50 mg/kg p.o.) and serum lp-PLA2 activity before or 1, 3, 6, 12, 24 hours after administration was measured. (B). Serum lp-PLA2 activity was measured using spectrometry before and at the end of drug administration. **p<0.01 vs. vehicle at 6 weeks. and *p<0.05 vs. vehicle at 0 week.
Table 1.
Effects of inhibition of lp-PLA2 by darapladib on body weight (g), serum total cholesterol, triglyceride, HDL-C and LDL-C levels (mM) in ApoE-deficient mice.
Figure 2.
Inhibition of lp-PLA2 by darapladib decreases serum hs-CRP and IL-6 levels, but has no significant effects on the PAF level.
After 6 weeks of feeding, serum hs-CRP, IL-6 and PAF levels were determined using ELISA. *p<0.05 and **p<0.01 vs. vehicle.
Figure 3.
Inhibition of lp-PLA2 decreases the atherosclerotic area.
(A). Representative en face atherosclerotic aorta preparations stained with Sudan IV. (B). Comparison of plaque sizes between the vehicle and darapladib groups (N = 13 per group). The area stained with dye is expressed as a percentage of the total surface area. The mean is depicted as a single horizontal line.
Figure 4.
Composition of atherosclerotic plaques in the aortic sinus.
(A) and (B). Representative examples are provided for VSMC-Actin, macrophage antibody (Mac-2) and trichrome-stained aortic sinus sections. Arrows are indicative of representative regions staining positively for VSMCs and macrophages. The collagen regions are indicated in blue. The bar indicates 400 µm (A) and 200 µm (B), respectively. (C). Comparison of VSMC, macrophage and collagen content between the two groups (N = 7 per group), *p<0.05 and **p<0.01 vs. vehicle.
Figure 5.
Inhibition of lp-PLA2 attenuates inflammatory gene expression at the aortic arch and thoracic-abdominal aortas.
Lp-PLA2, MCP-1, ICAM-1, VCAM-1, TNF-α, MMP-2 and MMP-9 gene expression was determined using quantitative RT-PCR. N = 5 per group, *p<0.05, and **p<0.01 vs. vehicle.