Abnormal preponderance of sialylated apolipoprotein CIII in triglyceride rich lipoproteins in type V hyperlipoproteinemia

Triglyceride rich lipoproteins contain apolipoproteins (apo) CII and CIII. Apo CII and CIII activate and inhibit tissue lipoprotein lipase, respectively. Apo CIII is a glycoprotein containing 0, 1 or 2 moles of sialic acid (designated apo CIII₀, CIII₁ and CIII₂, respectively). This study was designed to determine whether an abnormal distribution of these biologically active apoproteins occurred in triglyceride rich lipoproteins isolated from hypertriglyceridemic individuals. Triglyceride rich lipoproteins were isolated by preparative ultracentrifugation from 10 patients with primary type V hyperlipoproteinemia, eight patients with primary type IV hyperlipoproteinemia, and 11 normal healthy normolipidemic matched control subjects. After delipidation with tetramethyl urea, apo CII and CIII subspecies were separated by analytical isoelectric focussing with a pl range between 3.5 and 5.0. This technique allows a clear separation of apo CIII₀ from its sialylated subspecies and also from apo CII. The ratios of the individual apo CIII subspecies to each other and to apo CII were calculated from densitometric scanning of the stained gels. Desialylated apo CIII₀ comprised 3.3 ± 1.9% (M ± SD.) of total apo CIII in patients with type V hyperlipoproteinemia and was significantly lower (p = 0.0001) than the proportion found in normal subjects (14.3 ± 5.9%) and patients with primary type IV hyperlipoproteinemia (16.7 ± 6.2%). Apo CIII₁ comprised 62.4 ± 5.9% of total apo CIII in type V patients being significantly higher than that in normal subjects (52.6 ± 6.9%; p = 0.003) and patients with primary type IV hyperlipoproteinemia (47.1 ± 3.7%; p = 0.0001). Apo CIII₂ as percent of total apo CIII was similar in the three groups. The distribution of the apo CIII subspecies in patients with primary type IV hyperlipoproteinemia was similar to control subjects. In patients with type V hyperlipoproteinemia, the ratio of apo CIII₀; CII (0.11 ± 0.05) was significantly lower than normal (0.47 ± 0.26; p = 0.002), and also lower than the mean ratio observed in patients with primary type IV hyperlipoproteinemia (0.60 ± 0.25; p = 0.0001). Apo CIII₁;CII ratio in type V hyperlipoproteinemia (2.24 ± 0.58) was significantly higher than normal (1.64 ± 0.41; p = 0.02) and type IV hyperlipoproteinemia (1.67 ± 0.32; p = 0.047). Apo CIII₂:CII ratio was similar in the three groups. Total apo CIII:CII ratio in types IV and V (3.5 ± 0.86 and 3.55 ± 0.66, respectively) was higher than normal (3.15 ± 0.83), but the differences were not statistically significant. These data indicate that type V hyperlipoproteinemia is associated with an abnormal preponderance of sialylated to the desialylated apo CIII in triglyceride rich lipoproteins. Further work is needed to define the precise mechanism(s) responsible for this abnormality.