Impact of Oxidised Very Low-Density Lipoproteins on Endothelial Cell Viability and Migration: Implications for Vascular Repair

Background: Population studies consistently demonstrate a direct relationship between triglyceride levels and cardiovascular risk. The influence of triglyceride rich lipoproteins on the artery wall have not been well characterised. Here, we investigated the ex vivo effects of very low-density lipoproteins (VLDL) on vascular endothelial cells. Methods: VLDL was extracted from plasma of healthy human subjects by ultracentrifugation and modified by copper induced oxidation or glycation. The impact of co-incubation of native, oxidised and glycated VLDL (0-100 μg/ml) with human umbilical vein endothelial cells (HUVECs) for 12 hours on cellular viability was assessed using a colorimetric WST-1 assay and cellular migration using a scratch assay (50 μg/ml). These experiments were repeated following co-incubation of HUVECs with high-density lipoproteins isolated from healthy human subjects. Results: Oxidised, but not native or glycated VLDL, inhibited HUVECs viability by 15% (p<0.05) at concentrations greater than 50 μg/ml. In a similar fashion, oxidised, but not native or glycated VLDL, reduced HUVECs migration by 28% (p<0.05) compared with untreated HUVECs. Co-incubation of HUVECs with native HDL reduced the impact of oxidised VLDL on HUVEC viability by 21% (p<0.05). Conclusions: Oxidation of VLDL results in impairment of endothelial cell viability and migration, providing an important adverse mechanistic role of triglyceride rich lipoproteins in vascular repair. The ability of co-incubation with HDL to inhibit this effect provides another potential mechanism by which HDL exerts atheroprotective effects.