The density distribution of electronegative LDL [LDL( ؊ )], a cytotoxic and inflammatory fraction of LDL present in plasma, was studied in 10 normolipemic (NL), 6 FH, and 11 hypertriglyceridemic (HTG) subjects. Six LDL subclasses of increased density (LDL1 to LDL6) were isolated by density-gradient ultracentrifugation (DGU). NL and FH subjects showed prevalence of light LDL, whereas HTG subjects showed prevalence of dense LDL. LDL( ؊ ) proportion was determined from total LDL or LDL-density subclasses by anion-exchange chromatography. LDL from FH patients had increased LDL( ؊ ) (35.1 ؎ 9.9%) compared with LDL from NL and HTG subjects (9.4 ؎ 2.3% and 12.3 ؎ 4.3%, respectively). Most LDL( ؊ ) was contained in dense subclasses in NL (LDL4-6, 67.7 ؎ 3.1%) whereas most of LDL( ؊ ) from FH patients were contained in light LDL subclasses (LDL1-3) (86.2 ؎ 1.6%). In these subjects, simvastatin therapy decreased LDL( ؊ ) to 28.2 ؎ 6.7% and 21.2 ؎ 5.6% at 3 and 6 months of treatment, respectively, due mainly to decreases in light LDL subclasses. In HTG subjects, half LDL( ؊ ) was contained in dense LDL subclasses (LDL4-6, 46.1 ؎ 2.0%). Non-denaturing acrylamide gradient gel electrophoresis concurred with DGU data, as LDL( ؊ ) from NL showed a single band of lower size than non-electronegative LDL [LDL( ؉ )], whereas LDL( ؊ ) from FH and HTG presented bands of greater size than its respective LDL( ؉ ). These results reveal the existence of light and dense LDL( ؊ ), indicate that hyperlipemia could promote the formation of light LDL( ؊ ) and suggest that LDL( ؊ ) could have different origins. -Sánchez-Quesada,
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