Lipoprotein Morphology in Some LCAT-Deficient States

Abstract

A situation of maximal triglyceride (TG) hydrolysis was generated in normals and patients with type III hyperlipoproteinemia by a large oral fat load and subsequent heparin administration one hour after the fat meal. Lipoprotein fractions [chylomicrons, very low density lipoproteins (VLDL), low density lipoproteins (LDL₁ d 1.006-1.019, LDL₂ d 1.019-1.063), and high density lipoproteins (HDL₂ d 1.063-1.125, HDL, d 1.125-1.25)| were obtained by zonal or preparative ultracentrifugation and subsequent chromatography on 2% agarose. Electron microscopy was performed on full plasma and lipoprotein fractions by using the techniques of negative staining, freeze etching, shadowing and scanning electron microscopy (SEM). The lipoprotein morphology thus obtained was compared with that of type I hyperlipoproteinemia and of Zieve's syndrome. All conditions investigated had some abnormal lipoprotein structures in com mon: 1) Liposome-like particles (500-4000 Å) in the intermediate molecular weight (IMW) fraction of d 1.006-1.063.2) Disc-shaped structures (150-1000 Å) tending to aggregate in stacks and rouleaux upon concentration in LDL₂ and HDL₂. 3) Flattened, translucent and mostly round structures (200-3500 Å), some with a small globular area of electron dense lipid (all density classes). 4) Sword-like structures (1000- > 10000 Å) representing macrocrystalline free cholesterol (FC) in large molecular weight (LMW) subfractions of d < 1.019.5). Small, edgy and rod-like particles (150-500 Å), probably consisting of microcrystalline cholesterol in fractions of d < 1.063. All structures observed represent different physical-chemical arrangements of excess surface lipid. The appearance of large amounts of crystalline structures, 4) and 5), seems to depend on the presence of phospholipase and/or cholesterol ester hydrolase activity (Zieve's syndrome) which generates an excess of FC over phospholipid (PL), while particles described under 3) and 2) predominate when roughly equimolar amounts of FC and PL accumulate, as is the case in 'pure' LCAT-deficiency.

Key Words:

• cholesterol crystal
• electron microscopy
• hyperlipoproteinemia
• lipoprotein lipase
• liposome
• liver lipase
• LP-X
• phospholipase
• triglyceride-rich lipoprotein
• Zieve's syndrome