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- W2493233553 abstract "Background: Monocyte-mediated inflammation is a major mechanism of myocardial ischemia-reperfusion (IR) injury and cardiac remodeling. However, no anti-inflammatory therapy has been developed for clinical myocardial IR injury. Pioglitazone, a peroxisome proliferator-activated receptor (PPAR)γ agonist, has unique anti-inflammatory effects on monocyte/macrophage. Here we tested the hypothesis that nanoparticle-mediated targeting of pioglitazone into cardiomyocytes and inflammatory monocytes ameliorates IR injury and cardiac remodeling in preclinical animal models. Methods and Results: We formulated poly (lactic acid/glycolic acid) nanoparticle containing pioglitazone (Pio-NPs). In mouse IR model, nanoparticles were delivered predominantly to circulating monocytes and to cardiomyocytes and macrophages in the IR heart. Intravenous treatment with Pio-NPs containing ≥0.1 mg/kg of pioglitazone at the time of reperfusion reduced IR injury, which was canceled by the pretreatment with PPARγ antagonist GW9662 (Fig. A). In contrast, pioglitazone solution at doses up to 3.0 mg/kg showed no therapeutic effects (Fig. A). Pio-NPs reduced inflammatory gene expression and inhibited the recruitment of Ly6Chigh inflammatory monocytes into IR heart (Fig. B). Pio-NPs showed no therapeutic effects in mice lacking CCR2. In a mouse model of myocardial infarction, intravenous treatment with Pio-NPs for 3 days after LAD ligation attenuated cardiac remodeling, improved cardiac function, and reduced recruitment of macrophage and polarization of macrophages toward M2 phenotype (Fig. C, D). Finally, in a mini-pig model of myocardial IR injury, Pio-NPs induced cardioprotection from IR injury, indicating the pre-clinical proof of concept. Conclusion: Nanoparticle-mediated targeting of pioglitazone into cardiomyocytes and monocytes can be developed as a novel modality that offers organ protection by antagonizing monocyte-mediated inflammation in acute MI." @default.
- W2493233553 created "2016-08-23" @default.
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- W2493233553 date "2015-11-10" @default.
- W2493233553 modified "2023-09-24" @default.
- W2493233553 title "Abstract 17056: Nanoparticles-mediated Targeting of Pioglitazone Reduces Myocardial Ischemia-reperfusion Injury and Cardiac Remodeling by Antagonizing Monocyte-mediated Inflammation in Preclinical Animal Models" @default.
- W2493233553 doi "https://doi.org/10.1161/circ.132.suppl_3.17056" @default.
- W2493233553 hasPublicationYear "2015" @default.
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