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

Kazuo Sonoki, Masanori Iwase, Shigehiro Ohdo, Ichiro Ieiri, Yutaka Takata, Takanari Kitazono

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Abstract

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.

Original languageEnglish
Pages (from-to)489-496
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume64
Issue number6
DOIs
Publication statusPublished - Jun 30 2014

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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