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

研究成果: ジャーナルへの寄稿記事

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抄録

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.

元の言語英語
ページ(範囲)489-496
ページ数8
ジャーナルJournal of Cardiovascular Pharmacology
64
発行部数6
DOI
出版物ステータス出版済み - 6 30 2014

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Secretory Phospholipase A2
Hydroxymethylglutaryl-CoA Reductase Inhibitors
LDL Lipoproteins
Endothelial Cells
Tumor Necrosis Factor-alpha
Human Umbilical Vein Endothelial Cells
Lysophosphatidylcholines
Chemokine CCL2
Messenger RNA
Small Interfering RNA
Group V Phospholipases A2
rho-Associated Kinases
Phospholipases A2
human CCL2 protein
Phosphatidylcholines
Transfection
Proteins

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

これを引用

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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.",
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T1 - Statin inhibits the expression of secretory phospholipase A2 and subsequent monocyte chemoattractant protein-1 in human endothelial cells

AU - Sonoki, Kazuo

AU - Iwase, Masanori

AU - Ohdo, Shigehiro

AU - Ieiri, Ichiro

AU - Takata, Yutaka

AU - Kitazono, Takanari

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AB - 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.

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