Antiinflammatory and antiarteriosclerotic effects of pioglitazone

Minako Ishibashi, Kensuke Egashira, Hiasa Ken-Ichi, Shuujirou Inoue, Weihua Ni, Qingwei Zhao, Makoto Usui, Shiro Kitamoto, Toshihiro Ichiki, Akira Takeshita

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Peroxisome proliferator-activated receptor-γ (PPARγ) ligands are widely used in patients with insulin resistance and diabetes. Because coronary artery disease is a major complication for such patients, it is important to determine the effects of PPARγ activation on arteriosclerosis. Long-term inhibition of endothelial NO synthesis by administration of Nω-nitro-L-arginine methyl ester (L-NAME) to rats induces coronary vascular inflammation (monocyte infiltration, monocyte chemoattractant protein-1 [MCP-1] expression) and subsequent arteriosclerosis. We examined the effects of pioglitazone (a PPARγ ligand) in this rat model to determine whether PPARγ activation with pioglitazone inhibits arteriosclerosis by its indirect effects on metabolic conditions or by direct effects on the cells participating to the pathogenesis of arteriosclerosis. We found that pioglitazone did not affect metabolic states, systolic blood pressure, or serum NO levels, but did prevent the L-NAME-induced coronary inflammation and arteriosclerosis. Pioglitazone did not reduce local expression of MCP-1 but markedly attenuated increased expression of the MCP-1 receptor C-C chemokine receptor 2 (CCR2) in lesional and circulating monocytes. PPARγ activation with pioglitazone prevented coronary arteriosclerosis, possibly by its antiinflammatory effects (downregulation of CCR2 in circulating monocytes). Inhibition of the CCR2-mediated inflammation may represent novel antiinflammatory actions of pioglitazone beyond improvement of metabolic state.

Original languageEnglish
Pages (from-to)687-693
Number of pages7
JournalHypertension
Volume40
Issue number5
DOIs
Publication statusPublished - Nov 1 2002

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pioglitazone
Peroxisome Proliferator-Activated Receptors
Anti-Inflammatory Agents
Arteriosclerosis
Chemokine Receptors
C Chemokines
Coronary Artery Disease
Monocytes
Chemokine CCL2
NG-Nitroarginine Methyl Ester
Inflammation
CCR2 Receptors
Blood Pressure
Ligands
CC Chemokines
Blood Vessels
Insulin Resistance
Down-Regulation

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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Antiinflammatory and antiarteriosclerotic effects of pioglitazone. / Ishibashi, Minako; Egashira, Kensuke; Ken-Ichi, Hiasa; Inoue, Shuujirou; Ni, Weihua; Zhao, Qingwei; Usui, Makoto; Kitamoto, Shiro; Ichiki, Toshihiro; Takeshita, Akira.

In: Hypertension, Vol. 40, No. 5, 01.11.2002, p. 687-693.

Research output: Contribution to journalArticle

Ishibashi, M, Egashira, K, Ken-Ichi, H, Inoue, S, Ni, W, Zhao, Q, Usui, M, Kitamoto, S, Ichiki, T & Takeshita, A 2002, 'Antiinflammatory and antiarteriosclerotic effects of pioglitazone', Hypertension, vol. 40, no. 5, pp. 687-693. https://doi.org/10.1161/01.HYP.0000036396.64769.C2
Ishibashi, Minako ; Egashira, Kensuke ; Ken-Ichi, Hiasa ; Inoue, Shuujirou ; Ni, Weihua ; Zhao, Qingwei ; Usui, Makoto ; Kitamoto, Shiro ; Ichiki, Toshihiro ; Takeshita, Akira. / Antiinflammatory and antiarteriosclerotic effects of pioglitazone. In: Hypertension. 2002 ; Vol. 40, No. 5. pp. 687-693.
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