Induction of scavenger receptor class B type I is critical for simvastatin enhancement of high-density lipoprotein-induced anti-inflammatory actions in endothelial cells

Takao Kimura, Chihiro Mogi, Hideaki Tomura, Atsushi Kuwabara, Doon Soon Im, Koichi Sato, Hitoshi Kurose, Masami Murakami, Fumikazu Okajima

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Changes in plasma lipoprotein profiles, especially low levels of high-density lipoprotein (HDL), are a common biomarker for several inflammatory and immune diseases, including atherosclerosis and rheumatoid arthritis. We examined the effect of simvastatin on HDL-induced anti-inflammatory actions. HDL and sphingosine 1-phosphate (S1P), a bioactive lipid component of the lipoprotein, inhibited TNF α-induced expression of VCAM-1, which was associated with NO synthase (NOS) activation, in human umbilical venous endothelial cells. The HDL- but not S1P-induced anti-inflammatory actions were enhanced by a prior treatment of the cells with simvastatin in a manner sensitive to mevalonic acid. Simvastatin stimulated the expression of scavenger receptor class B type I (SR-BI) and endothelial NOS. As for S1P receptors, however, the statin inhibited the expression of S1P3 receptor mRNA but caused no detectable change in S1P1 receptor expression. The reconstituted HDL, a stimulator of SR-BI, mimicked HDL actions in a simvastatin-sensitive manner. The HDL- and reconstituted HDL-induced actions were blocked by small interfering RNA specific to SR-BI regardless of simvastatin treatment. The statin-induced expression of SR-BI was attenuated by constitutively active RhoA and small interfering RNA specific to peroxisome proliferator-activated receptor-α. Administration of simvastatin in vivo stimulated endothelial SR-BI expression, which was accompanied by the inhibition of the ex vivo monocyte adhesion in aortas from TNF α-injected mice. In conclusion, simvastatin induces endothelial SR-BI expression through a RhoA-and peroxisome proliferator-activated receptor-α-dependent mechanism, thereby enhancing the HDL-induced activation of NOS and the inhibition of adhesion molecule expression.

Original languageEnglish
Pages (from-to)7332-7340
Number of pages9
JournalJournal of Immunology
Volume181
Issue number10
DOIs
Publication statusPublished - Nov 15 2008

Fingerprint

CD36 Antigens
Simvastatin
HDL Lipoproteins
Anti-Inflammatory Agents
Endothelial Cells
Lysosphingolipid Receptors
Nitric Oxide Synthase
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Peroxisome Proliferator-Activated Receptors
Small Interfering RNA
Lipoproteins
Umbilicus
Mevalonic Acid
Vascular Cell Adhesion Molecule-1
Immune System Diseases
Aorta
Monocytes
Rheumatoid Arthritis
Atherosclerosis
Biomarkers

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Induction of scavenger receptor class B type I is critical for simvastatin enhancement of high-density lipoprotein-induced anti-inflammatory actions in endothelial cells. / Kimura, Takao; Mogi, Chihiro; Tomura, Hideaki; Kuwabara, Atsushi; Im, Doon Soon; Sato, Koichi; Kurose, Hitoshi; Murakami, Masami; Okajima, Fumikazu.

In: Journal of Immunology, Vol. 181, No. 10, 15.11.2008, p. 7332-7340.

Research output: Contribution to journalArticle

Kimura, Takao ; Mogi, Chihiro ; Tomura, Hideaki ; Kuwabara, Atsushi ; Im, Doon Soon ; Sato, Koichi ; Kurose, Hitoshi ; Murakami, Masami ; Okajima, Fumikazu. / Induction of scavenger receptor class B type I is critical for simvastatin enhancement of high-density lipoprotein-induced anti-inflammatory actions in endothelial cells. In: Journal of Immunology. 2008 ; Vol. 181, No. 10. pp. 7332-7340.
@article{5a32699852754624bb1744d69ae6829d,
title = "Induction of scavenger receptor class B type I is critical for simvastatin enhancement of high-density lipoprotein-induced anti-inflammatory actions in endothelial cells",
abstract = "Changes in plasma lipoprotein profiles, especially low levels of high-density lipoprotein (HDL), are a common biomarker for several inflammatory and immune diseases, including atherosclerosis and rheumatoid arthritis. We examined the effect of simvastatin on HDL-induced anti-inflammatory actions. HDL and sphingosine 1-phosphate (S1P), a bioactive lipid component of the lipoprotein, inhibited TNF α-induced expression of VCAM-1, which was associated with NO synthase (NOS) activation, in human umbilical venous endothelial cells. The HDL- but not S1P-induced anti-inflammatory actions were enhanced by a prior treatment of the cells with simvastatin in a manner sensitive to mevalonic acid. Simvastatin stimulated the expression of scavenger receptor class B type I (SR-BI) and endothelial NOS. As for S1P receptors, however, the statin inhibited the expression of S1P3 receptor mRNA but caused no detectable change in S1P1 receptor expression. The reconstituted HDL, a stimulator of SR-BI, mimicked HDL actions in a simvastatin-sensitive manner. The HDL- and reconstituted HDL-induced actions were blocked by small interfering RNA specific to SR-BI regardless of simvastatin treatment. The statin-induced expression of SR-BI was attenuated by constitutively active RhoA and small interfering RNA specific to peroxisome proliferator-activated receptor-α. Administration of simvastatin in vivo stimulated endothelial SR-BI expression, which was accompanied by the inhibition of the ex vivo monocyte adhesion in aortas from TNF α-injected mice. In conclusion, simvastatin induces endothelial SR-BI expression through a RhoA-and peroxisome proliferator-activated receptor-α-dependent mechanism, thereby enhancing the HDL-induced activation of NOS and the inhibition of adhesion molecule expression.",
author = "Takao Kimura and Chihiro Mogi and Hideaki Tomura and Atsushi Kuwabara and Im, {Doon Soon} and Koichi Sato and Hitoshi Kurose and Masami Murakami and Fumikazu Okajima",
year = "2008",
month = "11",
day = "15",
doi = "10.4049/jimmunol.181.10.7332",
language = "English",
volume = "181",
pages = "7332--7340",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

TY - JOUR

T1 - Induction of scavenger receptor class B type I is critical for simvastatin enhancement of high-density lipoprotein-induced anti-inflammatory actions in endothelial cells

AU - Kimura, Takao

AU - Mogi, Chihiro

AU - Tomura, Hideaki

AU - Kuwabara, Atsushi

AU - Im, Doon Soon

AU - Sato, Koichi

AU - Kurose, Hitoshi

AU - Murakami, Masami

AU - Okajima, Fumikazu

PY - 2008/11/15

Y1 - 2008/11/15

N2 - Changes in plasma lipoprotein profiles, especially low levels of high-density lipoprotein (HDL), are a common biomarker for several inflammatory and immune diseases, including atherosclerosis and rheumatoid arthritis. We examined the effect of simvastatin on HDL-induced anti-inflammatory actions. HDL and sphingosine 1-phosphate (S1P), a bioactive lipid component of the lipoprotein, inhibited TNF α-induced expression of VCAM-1, which was associated with NO synthase (NOS) activation, in human umbilical venous endothelial cells. The HDL- but not S1P-induced anti-inflammatory actions were enhanced by a prior treatment of the cells with simvastatin in a manner sensitive to mevalonic acid. Simvastatin stimulated the expression of scavenger receptor class B type I (SR-BI) and endothelial NOS. As for S1P receptors, however, the statin inhibited the expression of S1P3 receptor mRNA but caused no detectable change in S1P1 receptor expression. The reconstituted HDL, a stimulator of SR-BI, mimicked HDL actions in a simvastatin-sensitive manner. The HDL- and reconstituted HDL-induced actions were blocked by small interfering RNA specific to SR-BI regardless of simvastatin treatment. The statin-induced expression of SR-BI was attenuated by constitutively active RhoA and small interfering RNA specific to peroxisome proliferator-activated receptor-α. Administration of simvastatin in vivo stimulated endothelial SR-BI expression, which was accompanied by the inhibition of the ex vivo monocyte adhesion in aortas from TNF α-injected mice. In conclusion, simvastatin induces endothelial SR-BI expression through a RhoA-and peroxisome proliferator-activated receptor-α-dependent mechanism, thereby enhancing the HDL-induced activation of NOS and the inhibition of adhesion molecule expression.

AB - Changes in plasma lipoprotein profiles, especially low levels of high-density lipoprotein (HDL), are a common biomarker for several inflammatory and immune diseases, including atherosclerosis and rheumatoid arthritis. We examined the effect of simvastatin on HDL-induced anti-inflammatory actions. HDL and sphingosine 1-phosphate (S1P), a bioactive lipid component of the lipoprotein, inhibited TNF α-induced expression of VCAM-1, which was associated with NO synthase (NOS) activation, in human umbilical venous endothelial cells. The HDL- but not S1P-induced anti-inflammatory actions were enhanced by a prior treatment of the cells with simvastatin in a manner sensitive to mevalonic acid. Simvastatin stimulated the expression of scavenger receptor class B type I (SR-BI) and endothelial NOS. As for S1P receptors, however, the statin inhibited the expression of S1P3 receptor mRNA but caused no detectable change in S1P1 receptor expression. The reconstituted HDL, a stimulator of SR-BI, mimicked HDL actions in a simvastatin-sensitive manner. The HDL- and reconstituted HDL-induced actions were blocked by small interfering RNA specific to SR-BI regardless of simvastatin treatment. The statin-induced expression of SR-BI was attenuated by constitutively active RhoA and small interfering RNA specific to peroxisome proliferator-activated receptor-α. Administration of simvastatin in vivo stimulated endothelial SR-BI expression, which was accompanied by the inhibition of the ex vivo monocyte adhesion in aortas from TNF α-injected mice. In conclusion, simvastatin induces endothelial SR-BI expression through a RhoA-and peroxisome proliferator-activated receptor-α-dependent mechanism, thereby enhancing the HDL-induced activation of NOS and the inhibition of adhesion molecule expression.

UR - http://www.scopus.com/inward/record.url?scp=58149188481&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149188481&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.181.10.7332

DO - 10.4049/jimmunol.181.10.7332

M3 - Article

C2 - 18981156

AN - SCOPUS:58149188481

VL - 181

SP - 7332

EP - 7340

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 10

ER -