Metal- and Oxidant-Induced Aggregation Dynamics of aLDL: Dependence on Isomerization and Saturation of Fatty Acids

The effects of isomerization and saturation on the aggregation of artificial low-density lipoprotein (aLDL) models were investigated by kinetic tracking. The models were precisely engineered with defined cis- or trans-unsaturated and saturated fatty acid configurations in both surface phospholipids and core cholesteryl esters (CEs). Aggregation was compared under two types of stimuli: metal ions and radical oxidation. Under metal ion induction, aLDL aggregation occurred via neutralization of surface negative charges and metal ion-mediated bridging. trans-Unsaturated and saturated phospholipids packed more tightly on the LDL surface than their cis-counterparts, thereby increasing the aggregation propensity. In contrast, under radical oxidation induction, cis-phospholipids on the aLDL surface were more readily oxidized than trans-unsaturated and saturated phospholipids, leading to surface defects and fusion. Notably, neither cis- nor trans-unsaturated/saturated core CEs significantly affected LDL aggregation under either metal ion or radical oxidation conditions. These findings may help to clarify the molecular mechanisms of LDL oxidation and aggregation in humans.