Submitted on May 23, 2006
Revised on February 20, 2007
Accepted on February 27, 2007
Effects of apoA-I/phosphatidylcholine discs on charge-based LDL subfractions as characterized by capillary isotachophoresis
Bo Zhang, Yoshinari Uehara, Satoru Hida, Shin-ichiro Miura, David L. Rainwater, Masaru Segawa, Koichiro Kumagai, Kerry-Anne Rye, and Keijiro Saku
Dept. of Cardiology, Fkuoka University, Fukuoka 814-0180
Corresponding Author: bozhang{at}fukuoka-u.ac.jp
Objective: Modified low-density lipoprotein (LDL) in human plasma including small, dense LDL and oxidized LDL carries a more negative charge than unmodified LDL and is atherogenic. We examined the effects of apolipoprotein (apo) A-I/phosphatidylcholine (POPC) discs on charge-based LDL subfractions as determined by capillary isotachophoresis (cITP). Methods and Results: Three normal healthy subjects and 7 patients with metabolic disorders were included in the study. LDL in human plasma was separated into two major subfractions, fast- and slow-migrating LDL (fLDL and sLDL), by cITP. Normal LDL was characterized by low fLDL, and mildly oxidized LDL in vitro and mildly modified LDL in human plasma were characterized by increased fLDL. Moderately oxidized LDL in vitro and moderately modified LDL in a patient with hypertriglyceridemia and HDL deficiency were characterized by both increased fLDL and a new LDL subfraction with a faster mobility than fLDL (vfLDL). cITP LDL subfractions with faster electrophoretic mobility (fLDL vs. sLDL; vfLDL vs. fLDL) were associated with an increased content of small, dense LDL. Incubation of a plasma fraction with d>1.019 g/mL (depleted of triglyceride-rich lipoproteins) in the presence of apoA-I/POPC discs at 37oC greatly decreased vfLDL and fLDL, but increased sLDL. Incubation of whole plasma from patients with an altered distribution of cITP LDL subfractions in the presence of apoA-I/POPC discs also greatly decreased fLDL, but increased sLDL. ApoA-I/POPC discs decreased the cITP fLDL level, the free cholesterol concentration, and platelet-activating factor acetylhydrolase activity in the small, dense LDL subclasses (d 1.040 - 1.063 g/mL) and increased the size of LDL. Conclusion: ApoA-I/POPC discs reduced charge-modified LDL in human plasma by remodeling cITP fLDL into sLDL subfractions.
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