Caspase-dependent apoptosis in THP-1 cells exposed to oxidized low-densitylipoproteins

Oxidized low-density lipoproteins (oxLDL) play a critical role in atherogen esis. We investigated the apoptotic process in human monocytic THP-1 cell l ine, exposed to oxLDL generated by treatment of native LDL either with hypo chlorous acid (HOC1), mainly affecting the protein moiety, or with copper s ulfate (CuSO4), mainly affecting the lipid moiety. After incubation with bo th types of oxLDL, we observed: (i) microscopy signs of apoptosis in THP-1 cells, (ii) a significant increase of apoptotic cells proportional to LDL p rotein concentration, either by annexin V or by cell cycle phase analysis w ith propodium iodide flow cytometry, (iii) a reduction of THP-1 cell apopto sis in presence of the caspase inhibitor Z-VAD.fmk, (iv) the resistance of THP-1 cells apoptosis after PMA-elicited differentiation. In conclusion, HO Cl-oxLDL are as potent as Cu-oxLDL to induce high rates of apoptosis in mon ocytes through a caspase-dependent pathway. Moreover, the resistance of dif ferentiated THP-1 cells to oxLDL-induced apoptosis is compatible with the h ypothesis that mature macrophages have prolonged survival and thereby enhan ce the atherogenic process, (C) 2000 Academic Press.