Table 1.
Composition properties of lipoprotein complexes.
Figure 1.
Schematic representation of the kinetic processes modeled.
(A) Synthesis of A- and B-particles and degradation via HDL and LDL receptors, respectively. (B) Influx of peripheral cholesterol (“C”) into A-particles via the ATP-binding cassette A1 (ABCA1) receptor and selective efflux of cholesteryl ester (“C”) by the scavenger receptor B1 (SR-B1). (C) Elementary processes of the cholesteryl ester transfer protein (CETP) mediating the exchange of triglycerides (“T”) and cholesteryl ester (“C”) between lipoprotein components. CETP(0), CETP(T), and CETP(C) represent non-lipid–bound, T- and C-loaded forms of CETP, respectively. (D, E) Exchange of apolipoproteins (“A,” “F”) among lipoprotein complexes via plasma pools (PoolA, PoolF). (F) Hydrolysis of triglycerides (“T”) from A- and B-particles by hepatic and/or lipoprotein lipase (HL, LPL).
Figure 2.
Stochastic versus deterministic simulation.
Density distributions of the concentration of the sum of lipoprotein components (mg/dl) obtained by using the Gillespie algorithm with different numbers of simulation steps (events) and by the iterative solution of the deterministic equation system. The density space (0.93–1.35 g/ml) was subdivided into 30 equally sized intervals.
Table 2.
Experimental lipoprotein composition data.
Table 3.
Model parameter values.
Figure 3.
Simulated versus clinically measured distribution of lipoprotein components over main density classes including sub-fractions of LDL1-6, HDL2b, HDL2a and HDL3.
x-axis: number of lipoprotein density fraction; y-axis: simulated (circles) versus clinically measured (rectangles) concentration values in mg/dl of Apolipoprotein A–I (A), Apolipoprotein B-100 (B), Sum of further apolipoproteins (C), Total cholesterol (D), Triglycerides (E, logarithm) and Phospholipids (F). The error bars show the standard deviation of the experimental values.
Figure 4.
Variation in the initial composition of B-particles.
The initial composition of B-particles, i.e. the molecule numbers of component F, C and T, was randomized. The filled black bars (x = 0) mark the default B-particle initial composition (initF = 10, initC = 2000, initT = 10000). A total of 100 different compositions (brown bars) were analyzed by independent simulation runs. The graphs are sorted by the euclidean distance (topmost sub-graph, black dashed line). The change in the error measure (distance between calculated and experimental lipoprotein distributions) relative to the value obtained for the default composition is shown in the topmost sub-graph (black continous line).
Figure 5.
High-resolution distribution of total cholesterol within main density classes including sub-fractions of LDL1-6, HDL2b, HDL2a, and HDL3.
Each density class was further decomposed into 5 equally sized sub-fractions, called hrDS (grey bars). x-axis: density in g/ml; y-axis: concentration of total cholesterol in mg/dl normalized to the density interval size.
Figure 6.
High-resolution distribution of lipoprotein components within main density classes including sub-fractions of LDL1-6, HDL2b, HDL2a, and HDL3.
Each density class was further decomposed into five equally sized sub-fractions, called hrDS (grey bars). x-axis: number of lipoprotein density subfraction; y-axis: concentration of apolipoprotein A–I (A), apolipoprotein B-100 (B), sum of further apolipoproteins (C), total cholesterol (D), triglycerides (E) and phospholipids (F) in mg/dl normalized to the density interval size.
Figure 7.
Variation in the distribution of hrDS cholesterol at moderately altered parameter values.
Alteration of the normal hrDS cholesterol distribution (grey bars) by (A) increasing and (B) decreasing the parameter value of the HydrolyzeB process by 10% of its normal value (black bars). x-axis: metrical density intervals in g/ml; y-axis: concentration of total cholesterol in mg/dl normalized to the density interval size.
Figure 8.
Calculated pathological distribution compared with calculated normal data for LDL receptor deficiency.
Distributions of the lipoprotein components in the main density classes including sub-fractions of LDL1-6, HDL2b, HDL2a and HDL3. x-axis: number of lipoprotein density fractions; y-axis: calculated pathological (squares) and calculated normal (circles) concentration values of apolipoprotein A–I (A), apolipoprotein B-100 (B), sum of further apolipoproteins (C), total cholesterol (D), triglycerides ([E], logarithm) and phospholipids (F) in mg/dl.
Figure 9.
Calculated pathological distribution compared with calculated normal data for LPL deficiency.
Distributions of the lipoprotein components in the main density classes including sub-fractions of LDL1-6, HDL2b, HDL2a, and HDL3. x-axis: number of lipoprotein density fractions; y-axis: calculated pathological (squares) and calculated normal (circles) concentration values of apolipoprotein A-I (A), apolipoprotein B-100 (B), sum of further apolipoproteins (C), total cholesterol (D), triglycerides ([E], logarithm), and phospholipids (F, logarithm) in mg/dl.
Figure 10.
Calculated pathological distribution compared with calculated normal data for ABCA1 deficiency.
Distributions of the lipoprotein components in the main density classes, including sub-fractions of LDL1-6, HDL2b, HDL2a and HDL3. x-axis: number of lipoprotein density fractions; y-axis: calculated pathological (squares) and calculated normal (circles) concentration values of of apolipoprotein A–I (A), apolipoprotein B-100 (B), sum of further apolipoproteins (C), total cholesterol (D), triglycerides ([E], logarithm), and phospholipids (F) in mg/dl.
Table 4.
Data for density calculation.