On the lipoprotein abnormality in type III hyperlipoproteinemia

Abstract

A B S T R A C T Two lipoprotein species were isolated by starch block electrophoresis from the very low density lipoproteins (VLDL) (St 20-400) of patients with type III hyperlipoproteinemia. One of these, a2-VLDL, had a content of lipid and protein and physical characteristics similar to VLDL from normal subjects or patients with other forms of hyperglyceridemia. The other species, 9-VLDL, contained more cholesterol and less triglyceride in relation to the protein, than normal VLDL. Only the apoprotein of low density lipoprotein was immunochemically detectable in the P-VLDL; the proteins in the a2-VLDL reacted with antisera specific for low density lipoprotein and high density lipoprotein. The electrophoretic mobility of P-VLDL was similar to that of low density lipoprotein and significantly less than that of a2-VLDL. Isolated P-VLDL had a lesser mean flotation rate than a2-VLDL, but both a2-and 8-VLDL were found throughout the Si 20-400 flotation range.The relative quantities of a2-and f-VLDL could be varied by changing the diet or by heparin administration. Most of the VLDL from type III patients on a high carbohydrate diet was in the a2-VLDL form. During fasting, caz-VLDL fell and P-VLDL increased becoming the predominant species of VLDL. Heparininduced acceleration of triglyceride clearance also increased p-VLDL and decreased a2-VLDL. These findings suggest a precursor-product relationship between the a2-and P-forms of VLDL. in most electrophoretic systems. On paper electrophoresis, VLDL1 occupy a pre-Pposition (1, 2) and on starch block (3) they migrate as a fairly homogeneous band in the position of a2-globulins. The composition of VLDL isolated by electrophoresis or preparative ultracentrifugation is usually quite reproducible, consisting of about 10, 12, and 65% by weight of protein, cholesterol, and triglyceride, respectively (4, 5). INTRODUCTIONA group of patients has recently been identified with an aberrant form of VLDL. This VLDL has an unusual electrophoretic mobility, extending from the jS-to the a2-zone on paper electrophoresis (2), and an abnormal composition, including significantly more cholesterol in proportion to triglyceride. The presence of such abnormal VLDL appears to be genetically determined and is associated with unique clinical features leading to its classification as type III hyperlipoproteinemia (2). The isolation from patients with this disorder of two distinct forms of VLDL, characterized by their electrophoretic mobility as p-VLDL and a2-VLDL, is described in this report. METHODS Patients12 patients with type III, 5 with type IV hyperlipoproteinemia, and 5 normal volunteers (aged 19-26), classified according to previously published criteria (2), were studied as in-patients at the National Institutes of Health Clinical Center. Each was fed two different diets. The "balanced low cholesterol diet" contained approximately 20, 40, and 40% of calories, respectively as protein, carbohydrate, and fat (P/S ratio of about 2.0), and less than 300 mg cholesterol per day. The "high carbohy...

Pre-beta-very low density lipoproteins as precursors of beta-very low density lipoproteins. A model for the pathogenesis of familial dysbetalipoproteinemia (type III hyperlipoproteinemia).

“…However, a problem confounding the interpretation of VLDL turnover studies in dysbetalipoproteinemia is the heterogeneity of the injected material. In particular, VLDL from dys-fl subjects contain pre-4-VLDL, which are larger and more triglyceride rich than fl-VLDL and may be precursors of (-VLDL (31)(32)(33)(34). The kinetics of pre-fl-VLDL and f3-VLDL after intravenous administration of ['4C]palmitate are consistent with a precursor-product relationship (34).…”

Kinetic model for production and metabolism of very low density lipoprotein triglycerides. Evidence for a slow production pathway and results for normolipidemic subjects.

“…The size of these tails should be even smaller for VLDL-TG. This is in contrast to the magnitude of the tail (frequently 30 (37,38). For any mixture of these two, involving a fraction (a) of (8-VLDL and fraction (1 -a) of VLDL from normals, the CH/TG ratio is given by:…”

Familial hyperlipoproteinemia type III: Deficiency of a specific apolipoprotein (APO E‐III) in the very‐low‐density lipoproteins

“…This lipoprotein has fl-instead of pre-/J-mobility in electrophoresis [I] and is rich in cholesterol [2] and in an arginine-rich apolipoprotein [3]. There is evidence that this lipoprotein is an intermediate in the catabolism of triglyceride-rich lipoproteins which accumulate in hyperlipoproteinemia type III [3].…”