Lp(a) and LDL induce apoptosis in human endothelial cells and in rabbit aorta: Role of oxidative stress

Background. Atherogenic lipoproteins cause injury to the vascular wall in t he early phase of atherogenesis. We assessed the effects of native (nLDL) a nd oxidized (oxLDL) low-density lipoprotein (LDL) and lipoprotein (a) [ip(a )] on O-2(-) formation and cell death in cultured human umbilical vein endo thelial cells (HUVECs) and rabbit aorta (RA). Methods ann Results. O-2(-) formation of HUVECs and RA segments was not inf luenced by nLDL, but was dose dependently increased by oxLDL and was modera tely increased by nLp(a). oxLp(a) was the most potent stimulus for O-2(-) f ormation, increasing it in HUVECs by 356% at 5 mu g/ml and in RA by 294% at 100 mu g/ml. Apoptosis was detected by DNA fragmentation and Annexin assay in HUVECs and by TUNEL staining in RA. Incubation of HUVECs and RA with ox LDL. but not nLDL, dose and time dependently induced apoptosis with only a minimal effect on necrosis. nLp(a) elicited a small but significant effect on apoptosis, whereas oxLp(a) induced apoptosis more potently than oxLDL in HUVECs and RA and caused necrotic cell death in HUVECs. Induction of apopt osis by oxLDL and oxLp(a) in RA was enhanced by the superoxide dismutase (S OD) inhibitor, diethyl-dithio-carbamate, and was blunted by SOD and catalas e in HUVECs and RA, suggesting that O-2(-) formation was involved. The conc entration of lysophosphatidylcholine, a lipoprotein oxidation product and s timulus for O-2(-) formation, was significantly enhanced by factor 5 in oxL DL and by factor 7 in oxLp(a) compared with native lipoproteins. Conclusion. Atherogenic lipoproteins stimulate O-2(-) formation and inducti on of apoptosis in HUVECs and RA, and may thereby influence the pathogenesi s of atherosclerosis.