The mechanism of oxidation-induced low-density lipoprotein aggregation: Ananalogy to colloidal aggregation and beyond?

Atherosclerosis is a disease initiated by lipoprotein aggregation and depos ition in artery walls. In this study, the de novo low-density lipoprotein a ggregation process was examined. Nine major intermediates were identified i n two stages of the aggregation process. In the aggregation stage, low-dens ity lipoprotein molecules aggregate and form nucleation units. The nucleati on units chain together and form linear aggregates. The linear aggregates b ranch and interact with one another, forming fractals. In the fusion stage, spatially adjacent nucleation units in the fractal fuse into curved membra ne surfaces, which, in turn, fuse into multilamellar or unilamellar vesicle s. Alternatively, some adjacent nucleation units in the fractals assemble i n a straight line and form rods. Subsequently, the rods flatten out into ro ugh and then into smooth ribbons. Occasionally, tubular membrane vesicles a re formed from the fractals. The aggregation stage seems to be analogous to colloidal aggregation and amyloid fiber formation. The fusion stage seems to be characteristic of the lipid-rich lipoproteins and is beyond colloidal aggregation and amyloid fiber formation.