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Background: Hypertriglyceridemia is associated with decreased HDL-cholesterol (HDL-C) and increased small dense LDL. In addition, small dense LDL is known to be susceptible to oxidation. Methods: We measured LDL particle size, using gradient gel electrophoresis, and malondialdehyde-modified LDL (MDA-LDL), using an ELISA, and investigated the association between triglyceride (TG) concentrations, LDL size, and MDA-LDL. Results: TG concentrations correlated negatively with the predominant LDL size (r = −0.650) and HDL-C concentration (r = −0.556). The relationship between TG concentration and LDL size, evaluated by measuring MDA-LDL, distinguished subgroups derived from four subfractions of TG concentrations and four distribution ranges of LDL size. These experiments indicated that there is a threshold for oxidation susceptibility at an LDL size of 25.5 nm and a TG concentration of 1500 mg/L. To investigate the relationship between LDL size, MDA-LDL concentration, and other lipids (TGs, HDL-C, apolipoprotein B, and total cholesterol), we evaluated them in control subjects and patients with diabetes mellitus or hypertriglyceridemia. When the size range for normal LDL was postulated to be 25.5 ≤ φ (LDL diameter) < 26.5 nm, the MDA-LDL concentration was significantly higher in the subgroups of patients with LDL in the size range 24.5 ≤ φ < 25.5 nm compared with patients with normal LDL. This result also suggests that the threshold is at a LDL size of 25.5 nm. Conclusion: The threshold for oxidation susceptibility coincided with the point of LDL size separation between the LDL subclass patterns A and B as an atherosclerotic risk.

Several reports have suggested that HDL has anti-oxidative actions. We investigated the relationship between HDL-cholesterol (HDL-C) and malondialdehyde-modified LDL (MDA-LDL) concentrations using enzyme linked immunosolvent assay. We divided our study subjects into four groups on the basis of concentrations of triglyceride (TG) and HDL-C by the following lipid profiles: serum TG < or = 1.69 mmol/L and HDL-C > or = 1.16 mmol/L (control group, n = 26); TG >1.69 and HDL-C < or = 1.16 (high TG group, n = 22); TG >1.69 and HDL-C < or = 0.91 (high TG & low HDL group, n = 67); TG < or = 1.69 and HDL-C < or = 0.91 (low HDL group, n = 21). MDA-LDL concentrations, MDA-LDL/apolipoprotein B (apo B) ratio, and LDL size were different between subjects in high TG & low HDL and control groups. MDA-LDL concentrations in both high TG and low HDL groups did not differ significantly from those in the control. However, MDA-LDL/apo B ratio in low HDL group was significantly higher than that in the control (P < 0.05). The MDA-LDL/apo B ratio reflects the extent of MDA modification of apo B in LDL. Therefore, our data suggest that as HDL-C concentrations fall, the extent of MDA modification per one LDL particle increases. Moreover, accompanied by high TG concentration, LDL size in subjects with lower HDL-C concentrations became smaller.

SUMMARY.It has been demonstrated that apolipoproteins found in cerebrospinal fluid (CSF) play an important role in lipid metabolism in the central nervous system (CNS). Previously we reported that CSF apo A-I levels increased with the severity of neurological damage in poliovirus-infected macaques. In the present study, apo A-I was quantitatively analysed in CSF from patients with or without neurological diseases. In controls, CSF apo A-I level was significantly higher in males; 3.83 (0.40) mg/L, mean (SEM) (n = 19) compared with females, 2.42 (0.26) mg/L (n= 23, P