Antiinflammatory and antiarteriosclerotic effects of pioglitazone

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

Research output: Contribution to journalArticlepeer-review

147 Citations (Scopus)


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
Issue number5
Publication statusPublished - Nov 1 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine


Dive into the research topics of 'Antiinflammatory and antiarteriosclerotic effects of pioglitazone'. Together they form a unique fingerprint.

Cite this