title: Statin inhibits the expression of secretory phospholipase A2 and subsequent monocyte chemoattractant protein-1 in human endothelial cells.
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 TNFα-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 TNFα-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.
authors.affiliation: *Department of Oral Health Management, School of Oral Health Sciences, Kyushu Dental University, Kitakyushu, Japan; †Diabetes Center, Hakujyuji Hospital, Fukuoka, Japan; ‡Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; §Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan; and ¶Division of General Internal Medicine, Department of Health Promotion, Science of Health Improvement, Kyushu Dental University, Kitakyushu, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sonoki
authors.forename: Masanori
authors.initials: M
authors.lastname: Iwase
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Ohdo
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ieiri
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takata
authors.forename: Takanari
authors.initials: T
authors.lastname: Kitazono
mesh_terms: D000577:Amides / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000235:genetics*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism; D054497:Phospholipases A2, Secretory / Q000235:genetics*; D011106:Polyisoprenyl Phosphates / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000577:Amides; D018932:Chemokine CCL2; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D011106:Polyisoprenyl Phosphates; D011725:Pyridines; D011804:Quinolines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; C108830:Y 27632; D054497:Phospholipases A2, Secretory; C108475:pitavastatin; C002963:geranylgeranyl pyrophosphate