Number of core lipids at the surface and contacts between proteins and different lipids.

<p>(A) Number of core lipids at the surface of particles (number of contacts between water and neutral lipid ester beads). When compared to the control simulation (MD-1), the total number of neutral lipids at the surface decreases in simulation MD-4 where the ratio of surface lipids (PC, SM, FCho and lysoPC) and apolipoprotein residues is highest. Bar numbers show the percentage of total neutral lipids at the surface. (B) The number of contacts (per amino acid) between apoA-I or apoA-II and different lipids in simulations. Notably, the affinity of apoA-I towards PC, SM, FCho, and lysoPC is stronger than apoA-IIs. However, the affinity of ApoA-II is stronger towards ChoE compared to apoA-I. Affinities toward TG are same for both apolipoproteins. Errors bars are standard deviations.</p

Clinical and biochemical characteristics of the study groups.

<p>Values are mean± SD;</p>#<p>p = 0.003 High Hcy vs Low Hcy at baseline;</p><p>*p<0.001 High Hcy vs Low Hcy and placebo at close out;</p><p>**p<0.05 Low Hcy vs placebo;</p><p>**p<0.05 High Hcy vs placebo; BMI = Body Mass Index; Hcy = homocysteine.</p

The effects of covariates on clusters of lipids.

<p>The effects of fenofibrate (F), placebo (P) and interaction of fenofibrate and Hcy level (I) are shown by box-plots for each cluster of lipids. The box plots show quartiles and 95% intervals of posterior mass of the effects; a posterior distribution above or below zero implies an effect is found. Positive fenofibrate effect indicates that both Low Hcy and High Hcy groups are upregulated by fenofibrate treatment. The combination of positive fenofibrate effect and negative interaction effect indicate that only the Low Hcy group is upregulated by fenofibrate treatment.</p

Radial distribution functions of different molecules and snapshots from simualtions.

<p>(A) Radial distribution functions for TG, ChoE, PC, apoA-II and apoA-I respect to the center of mass of HDL particle (MD-4). Distributions clearly indicate that apoA-II is more deeply buried into lipid matrix. Inset shows a 2 nm slice from the center of HDL particle. Blue molecule is apoA-I, grey and red spheres are PCs, green ones are TGs, and transparent and orange spheres are ChoEs. (B) Snapshots from simulation MD-4 showing the binding and conformation of apoA-II during simulation MD-4. Top snapshot is from the start of short vacuum simulation. Middle one is from the start of water simulation. Bottom one is from the end of simulation MD-4 showing V-conformation of apoA-II on the surface of HDL particle. PCs and SMs are rendered using grey spheres. Cholesteryl esters and free cholesterol molecules are rendered using orange and yellow spheres, respectively. ApoA-II is rendered using brown spheres and ApoA-I using blue spheres. Only backbone beads are rendered for clarity. Water and TG beads are not shown.</p

Molecular composition of different simulation runs.

<p>Molecular composition of different simulation runs.</p

The concentrations of individual lipid species in the different study groups.

<p>Individual lipids from different lipid classes are shown: (A) lysophosphatidyl choline, (B) sphingomyelin, (C) ethanolamine plasmalogen and (D) cholesteryl ester. Data are shown in mean±SEM for each lipid. Concentration values are expressed in µmol/l [lipid]/mg/dl [HDL protein]. Significance levels are shown as follows: * p<0.05 for Low Hcy group <i>vs.</i> placebo group; ** p<0.01 for Low Hcy group <i>vs.</i> placebo group; # p<0.05 for Low Hcy group <i>vs.</i> High Hcy group; ## p<0.01 for Low Hcy group <i>vs.</i> High Hcy group and ### p<0.001 for Low Hcy group <i>vs.</i> High Hcy group.</p

The effects of covariates on clinical variables.

<p>The effects fenofibrate (F), placebo (P) and interaction of fenofibrate and Hcy level (I) are shown by box-plots for each clinical variable. Positive fenofibrate effect indicates that both Low Hcy and High Hcy groups are upregulated by fenofibrate treatment. The combination of positive fenofibrate effect and positive interaction effect indicate that both Low Hcy and High Hcy groups are upregulated by fenofibrate treatment and for the High Hcy groups the effect is even stronger. The box plots show quartiles and 95% intervals of posterior mass of the effects; a posterior distribution above or below zero implies an effect is found. A positive effect (above zero) implies an upregulation, a negative effect (below zero) implies a down-regulation. Significant and almost significant effects are highlighted in red and blue, respectively.</p