Formation of apolipoprotein-specific high-density lipoprotein particles from lipid-free apolipoproteins A-I and A-II

Abstract

We have shown previously that apolipoprotein A (apoA)-I-containing high-density lipoprotein (HDL) particles are formed by the conjugation of lipid-free apoA-I with lipids derived from other lipoprotein fractions in a process dependent on non-esterified fatty acids, generated by the lipolysis of very-low-density lipoprotein (VLDL) or provided exogenously. In the present study, we show that this process is also able to generate HDL particles containing apoA-II (A-II HDL) and both apoA-I and apoA-II (A-I/A-II HDL). When lipid-free apoA-II was incubated with either VLDLs and lipoprotein lipase or LDLs and sodium oleate, a significant proportion of the apoA-II was recovered in the HDL density fraction. This was associated with the formation of several populations of HDL-sized particles with pre-β2 electrophoretic mobility, which contained phospholipids and unesterified cholesterol as their main lipid constituents. When both lipid-free apoA-I and lipid-free apoA-II were incubated with LDL and sodium oleate, both apolipoproteins were recovered in HDLs that contained phospholipids and unesterified cholesterol as their main lipids. Two populations of particles had diameters of 7.4 and 10.8 nm and pre-β2-migration; there was also a population of pre-β1-migrating particles of diameter 4.7 nm. ApoA-I and apoA-II were both present in the larger HDLs, whereas only apoA-I was present in the smaller particles. Immunoaffinity chromatography on an anti-(apoA-I)–Sepharose column revealed that 10–20% of the apoA-II resided in particles that also contained apoA-I. The majority of the A-I/A-II HDL were present in a population of pre-β2 particles of 10.8 nm diameter. These results in vitro illustrate a potential mechanism for the formation of HDLs containing both apoA-I and apoA-II.

Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to induce cholesterol efflux from human macrophage foam cells

“…The monocyte-derived macrophages were incubated in DMEM (pH 7.4) containing 25 g/ml of [ (7.5 ± 0.2 nm), a fi nding consistent with previous reports on the size of pre ␤ 1-HDL ( 30,31 ). To quantitatively determine the generation of pre ␤ -HDL, the HDL particles were analyzed by two-dimensional crossed-immunoelectrophoresis.…”

Beneficial changes in serum apo A-1 and its ratio to apo B and HDL in stable hyperlipidaemic subjects after Ramadan fasting in Kuwait

“…This may be due to the reported compositional changes in lipoproteins seen not only in hyperlipidaemia. These abnormalities in lipoprotein composition have also been reported in diabetes and impaired glucose tolerance (Contiero et al, 1998, Pietzsch et al, 1998, variant angina (Miwa et al, 1998), high circulating concentrations of nonesteri®ed fatty acids and obesity (Clay et al, 1999) and use of hypolipidaemic medication (Staels & Auwerx, 1998). Incidentally, about 25% (30% women, 18% men) of our patients were diabetic and about 70% (52% men and 84% women) were obese (BMI b 28.0 kgam 2 ) with 94% (100% women, 88% men) overweight (BMI b 25.0 kgam 2 ).…”

Phospholipids mediated conversion of HDLs generates specific apoA-II pre-β mobility particles

“…6B). These sizes overlap those of pre-b HDL A-II formed by the conjugation of lipid-free apoA-II with lipids derived either from cell membranes or other lipoproteins (11,36).…”