Statin inhibits the expression of secretory phospholipase A² and subsequent monocyte chemoattractant protein-1 in human endothelial cells

Phospholipase A₂ (PLA₂) changes the phosphatidylcholine contained in low-density lipoprotein (LDL) to lysophosphatidylcholine (LPC), which has various proatherogenic properties. We reported that tumor necrosis factor-alpha (TNFα) enhanced the expression of group V PLA₂ (sPLA₂-V) in human umbilical vein endothelial cells (HUVECs), and the LPC content in LDL and the monocyte chemoattractant protein-1 (MCP-1) expression were augmented when TNFa-stimulated HUVECs were incubated with LDL. Here, we observed that an HMG-CoA reductase inhibitor, pitavastatin, at the concentration of > 1 μM administered 12 hours before TNFα stimulation suppressed the enhancement of sPLA₂-V mRNA and protein. Pitavastatin also prevented the enhancement of the LPC content in LDL and the expression of MCP-1 mRNA when TNFα stimulated HUVECs were incubated with LDL. The administration of geranylgeranyl pyrophosphate restored the expression of sPLA₂- V mRNA and protein. The administration of the Rho kinase inhibitor Y-27632 and the transfection of small interfering RNA (siRNA) against sPLA₂-V before TNFα stimulation both diminished the TNFa-induced sPLA2-V mRNA expression. Therefore, Y-27632 and siRNA against sPLA2-V also prevented the enhancement of MCP-1 mRNA expression when TNFα stimulated HUVECs were incubated with LDL. Pitavastatin's inhibitory effect on the expression of sPLA₂-V induced by TNFα may be useful to prevent the proatherogenic modification of LDL.