We have cloned a prostacyclin (PGI2) stimulating factor (PSF), which stimulates PGI2 production by vascular endothelial cells. Previous study demonstrated the reduced PSF expression in the coronary arteries from the patients with ischemic heart disease. To clarify the mechanism of reduced PSF expression in atherosclerosis, we examined the effect of lysophosphatidylcholine (lysoPC), a main component of oxidized low density lipoprotein (LDL), on PSF expression in cultured vascular smooth muscle cells. LysoPC reduced PSF expression dose-dependently. Whereas neither phosphatidylcholine nor native LDL affects the PSF expression. Calphostin C, a protein kinase C (PKC) inhibitor, restored the reduction of PSF expression by lysoPC. These results suggest that lysoPC-induced reduction of PSF expression is mediated by PKC activation and is playing a role in the initiation and progression of atherosclerotic lesions.