Characterization of remnant-like particles isolated by immunoaffinity gel from the plasma of type III and type IV hyperlipoproteinemic patients

Abstract

Previous studies have investigated the potential atherogenicity and thrombogenicity of triglyceride-rich lipoprotein (TRL) remnants by isolating them from plasma within a remnant-like particle (RLP) fraction, using an immunoaffinity gel containing specific anti-apoB-100 and anti-apoA-I antibodies. In order to characterize lipoproteins in this RLP fraction and to determine to what extent their composition varies from one individual to another, we have used automated gel filtration chromatography to determine the size heterogeneity of RLP isolated from normolipidemic control subjects (n ‫؍‬ 8), and from type III (n ‫؍‬ 6) and type IV (n ‫؍‬ 9) hyperlipoproteinemic patients, who by selection had similarly elevated levels of plasma triglyceride (406 ؎ 43 and 397 ؎ 35 mg/dl, respectively). Plasma RLP triglyceride, cholesterol, apoB, apoC-III, and apoE concentrations were elevated 2-to 6-fold ( P Ͻ 0.05) in hyperlipoproteinemic patients compared to controls. RLP fractions of type III patients were enriched in cholesterol and apoE compared to those of type IV patients, and RLP of type IV patients were enriched in triglyceride and apoC-III relative to those of normolipidemic subjects. In normolipidemic subjects, the majority of RLP had a size similar to LDL or HDL. The RLP of hyperlipoproteinemic patients were, however, larger and were similar in size to TRL, or were intermediate in size (i.e., ISL) between that of TRL and LDL. Compared to controls, ISL in the RLP fraction of type III patients were enriched in apoE relative to apoC-III, whereas in type IV patients they were enriched in apoC-III relative to apoE. These results demonstrate that: 1 ) RLP are heterogeneous in size and composition in both normolipidemic and hypertriglyceridemic subjects, and 2 ) the apoE and apoC-III composition of RLP is different in type III compared to type IV hyperlipoproteinemic patients. -Marcoux, C., M. Tremblay, K. Nakajima, J. Davignon, and J. S. Cohn. Characterization of remnant-like particles isolated by immunoaffinity gel from the plasma of type III and type IV hyperlipoproteinemic patients.

Properties of triglyceride-rich and cholesterol-rich lipoproteins in the remnant-like particle fraction of human blood plasma

“…It should be noted that little of the apoA-I component of the unbound fraction (ϳ2 mg/dl) would likely be present in total plasma RLP, as a Mab to apoA-I is included, together with Mab JI-H, in the RLP reagent (2). Marcoux et al found only 0.3% of plasma apoA-I in plasma RLP from normolipidemic subjects (5).…”

“…Since that time, a considerable body of literature has supported the utility of RLP-C concentration as a risk marker for atherosclerotic disease (3). It has been recognized, however, that the test for RLP-C in particular includes not only the described fraction of TRL, but also certain lipoproteins of higher density (2,(4)(5)(6).…”

“…By contrast, more than 97% of the cholesterol in lipoproteins other than TRL in plasma from normolipidemic subjects is retained by the Mabs (JI-H and anti-apoA-I) that are utilized in the RLP test (4). In plasma from subjects with low TRL concentrations, however, these latter lipoproteins may comprise a major fraction of RLP (2,(4)(5)(6). Recent studies have shown that most non-TRL in the RLP fraction of plasma are of LDL size with relatively little contribution from HDL-sized particles (5,6).…”

“…In plasma from subjects with low TRL concentrations, however, these latter lipoproteins may comprise a major fraction of RLP (2,(4)(5)(6). Recent studies have shown that most non-TRL in the RLP fraction of plasma are of LDL size with relatively little contribution from HDL-sized particles (5,6). As separated by gel filtration chromatography, the LDL-sized lipoproteins in the RLP fraction are enriched in apoE and apoC-III as well as apoB-100 (5), and are slightly larger on average than bulk LDL (6).…”

“…Recent studies have shown that most non-TRL in the RLP fraction of plasma are of LDL size with relatively little contribution from HDL-sized particles (5,6). As separated by gel filtration chromatography, the LDL-sized lipoproteins in the RLP fraction are enriched in apoE and apoC-III as well as apoB-100 (5), and are slightly larger on average than bulk LDL (6). These and other observations have led to the suggestions that RLP-LDL have special properties (5) and may represent LDL-sized remnant lipoproteins (6).…”