| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
Objective―Inflammatory monocytes/macrophages produce various proteinases and induce rupture of atherosclerotic plaques. We have tested a hypothesis that nanoparticle-mediated delivery of peroxisome proliferator-activated receptor-γ agonist pioglitazone to monocytes/macrophages inhibits plaque ruptures.
Approach and Results―Poly(lactic-co-glycolic-acid) nanoparticles (NPs) were prepared for targeting delivery to monocytes/macrophages. Weekly intravenous administration of pioglitazone-NPs decreased buried fibrous caps, suggesting healed ruptures, in the brachiocephalic arteries of Apoe－/－ mice with a high-fat diet and angiotensin II infusion. Pioglitazone-NPs also inhibited the activity of proteases and decreased expression of inflammatory cytokines in macrophages.
Conclusions―Nanoparticle-mediated delivery of pioglitazone inhibited macrophage activation and plaque ruptures in ApoE-/- mice. These results demonstrate a promising strategy to prevent atherosclerotic plaque ruptures.
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