The oxidized phospholipids POVPC and PGPC inhibit growth and induce apoptosis in vascular smooth muscle cells.
Oxidized phospholipids, including 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) are typically present in oxidatively modified low density lipoprotein (oxLDL) and have been found in atherosclerotic lesions. These compounds are gaining increasing importance as inducers of different cellular responses like inflammation, proliferation, or cell death. The aim of this study was to elicit the type and outcome of the cellular response of vascular smooth muscle cells (VSMC) upon treatment with POVPC and PGPC. Both oxidized phospholipids led to inhibition of cell proliferation and showed cytotoxic effects in VSMC. Several morphological criteria, the presence of typical DNA fragments, and a phosphatidylserine shift towards the outer leaflet of the cell membrane revealed that apoptosis was the predominant mode of cell death. In all experiments, POVPC was found to be a more potent inducer of apoptosis than PGPC. Interestingly, in the presence of high levels of serum in the growth media the proapoptotic but not the antiproliferative effects of both oxidized phospholipids were abolished. Thus, we conclude that under low serum conditions both intact POVPC and PGPC are proapoptotic mediators. Under high serum conditions, these lipids are hydrolyzed and the resultant lipid mixture containing the degradation products is no longer apoptotic but antiproliferative. Thus, the direct and indirect effects of POVPC and PGPC on cell viability may account for the detrimental actions of oxLDL on VSMC.
Fruhwirth
Gilbert O
GO
Institute of Biochemistry, Graz University of Technology, Petersgasse 12/2, A-8010 Graz, Austria.
Moumtzi
Alexandra
A
Loidl
Alexandra
A
Ingolic
Elisabeth
E
Hermetter
Albin
A
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D005312:Fetal Blood; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D010084:Oxidation-Reduction; D010718:Phosphatidylserines / Q000378:metabolism; D010742:Phospholipid Ethers / Q000494:pharmacology*; D051381:Rats; D044967:Serum
C400184:1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine; C400185:1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine; D008077:Lipoproteins, LDL; D010718:Phosphatidylserines; D010742:Phospholipid Ethers; C099252:oxidized low density lipoprotein