Figure 1.
Effect of niacin, simvastatin and their combination on plasma lipid levels.
Plasma total cholesterol (A), triglycerides (B) and HDL-cholesterol levels were measured at various time points throughout the study. The average HDL-cholesterol levels were calculated for all the treatment groups (C). Lipoproteins were separated by FPLC and cholesterol was measured in the fractions after 18 weeks of treatment (D). (Simva, simvastatin; values are means ± SD; n = 15 per group; **P<0.01 and ***P<0.001 as compared to control; #P<0.05 and ###P<0.001 as compared to niacin+simvastatin).
Figure 2.
Effect of niacin on VLDL production and clearance.
To determine VLDL production, mice were injected with Trans35S label and tyloxapol and the accumulation of TG in plasma (A) and the production rate of VLDL-TG and apoB, as well as VLDL lipidation, defined as the ratio of VLDL-TG/apoB, were determined (B). To determine VLDL clearance, mice were injected with glycerol tri[3H]oleate- and [14C]cholesteryl oleate-labeled VLDL-like emulsion particles. Plasma 3H-activity was determined as percentage of the initial dose (C), and uptake of 3H-activity by various organs was determined as percentage of the injected dose per gram wet tissue (D). (BAT, brown adipose tissue; gonWAT, gonadal white adipose tissue; subWAT, subcutaneous white adipose tissue; visWAT, visceral white adipose tissue; values are means ± SD; n = 6 per group for VLDL production and n = 3–5 per group for VLDL clearance; *P<0.05 as compared to control).
Table 1.
The effect of niacin, simvastatin and their combination on plasma CETP activity after 4 and 18 weeks of treatment, as well as plasma CETP mass and hepatic CETP expression after 18 weeks of treatment.
Figure 3.
Effect of niacin, simvastatin and their combination on plaque morphology.
Representative images of hematoxylin-phloxine-saffron-stained atherosclerotic lesions in a cross section of the aortic root area for the control group (A), niacin group (B), simvastatin group (C) and the combination group (D) after 18 weeks of treatment.
Figure 4.
Effect of niacin, simvastatin and their combination on atherosclerosis development in aortic root area.
After 18 weeks of treatment, number of lesions (A), lesion severity (B), percentage undiseased segments (C) and total lesion area (D) were determined per cross section. Lesion severity was classified as mild (type I–III) and severe (type IV–V) lesions. (Simva, simvastatin; values are means ± SD; n = 15 per group; **P<0.01 and ***P<0.001 as compared to control; ##P<0.01 as compared to niacin+simvastatin).
Figure 5.
Effect of niacin, simvastatin and their combination on lesion composition.
Macrophage area (A) and SMC area (B) were determined for all lesions and calculated per cross section. To correct for lesion size, macrophage content (C), SMC content (D), as well as plaque stability index (ratio of collagen and SMC content to macrophage content) (E) were also calculated as a percentage of lesion area, specifically in severe lesions (Type IV–V). (Simva, simvastatin; SMC, smooth muscle cells; values are means ± SD; n = 15 per group; *P<0.05, **P<0.01 and ***P<0.001 as compared to control; #P<0.05, and ###P<0.001 as compared to niacin+simvastatin).
Figure 6.
Effect of niacin, simvastatin and their combination on monocyte adhesion and T cell number.
The number of monocytes adhering to the endothelium (A) and the number of T cells in the aortic root area (B) were determined per cross section. (Simva, simvastatin; values are means ± SD; n = 15 per group; **P<0.01; ***P<0.001 as compared to control; ###P<0.001 as compared to niacin+simvastatin).
Figure 7.
Correlation between plasma cholesterol exposure and lesion area.
The square root of the lesion area was plotted against total cholesterol exposure (A), nonHDL-cholesterol exposure (B) and HDL-cholesterol exposure (C). Linear regression analyses were performed. (Simva, simvastatin; n = 15 per group).
Figure 8.
Effect of niacin on reverse cholesterol transport.
[3H]-cholesterol-labeled macrophages were injected in control and niacin-treated mice and 3H activity was determined in plasma and HDL (A) and the liver 48 h after injection, as well as in feces collection between 0–48 h after injection (B). (Values are means ± SD; n = 8 per group; *P<0.05 and ** P<0.01 as compared to control).