Therapeutic effects of targeted PPARγ activation on inflamed high-risk plaques assessed by serial optical imaging in vivo

Jah Yeon Choi, Jiheun Ryu, Hyun Jung Kim, Joon Woo Song, Joo Hee Jeon, Dae Hee Lee, Dong Joo Oh, Dae Gab Gweon, Wang Yuhl Oh, Hongki Yoo, Kyeongsoon Park, Jin Won Kim

    Research output: Contribution to journalArticlepeer-review

    20 Citations (Scopus)


    Rationale: Atherosclerotic plaque is a chronic inflammatory disorder involving lipid accumulation within arterial walls. In particular, macrophages mediate plaque progression and rupture. While PPARγ agonist is known to have favorable pleiotropic effects on atherogenesis, its clinical application has been very limited due to undesirable systemic effects. We hypothesized that the specific delivery of a PPARγ agonist to inflamed plaques could reduce plaque burden and inflammation without systemic adverse effects. Methods: Herein, we newly developed a macrophage mannose receptor (MMR)-targeted biocompatible nanocarrier loaded with lobeglitazone (MMR-Lobe), which is able to specifically activate PPARγ pathways within inflamed high-risk plaques, and investigated its anti-atherogenic and anti-inflammatory effects both in in vitro and in vivo experiments. Results: MMR-Lobe had a high affinity to macrophage foam cells, and it could efficiently promote cholesterol efflux via LXRα-, ABCA1, and ABCG1 dependent pathways, and inhibit plaque protease expression. Using in vivo serial optical imaging of carotid artery, MMR-Lobe markedly reduced both plaque burden and inflammation in atherogenic mice without undesirable systemic effects. Comprehensive analysis of en face aorta by ex vivo imaging and immunostaining well corroborated the in vivo findings. Conclusion: MMR-Lobe was able to activate PPARγ pathways within high-risk plaques and effectively reduce both plaque burden and inflammation. This novel targetable PPARγ activation in macrophages could be a promising therapeutic strategy for high-risk plaques.

    Original languageEnglish
    Pages (from-to)45-60
    Number of pages16
    Issue number1
    Publication statusPublished - 2018


    • Lobeglitazone
    • Macrophage
    • PPARγ
    • Plaque
    • Serial imaging
    • Targeted

    ASJC Scopus subject areas

    • Medicine (miscellaneous)
    • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)


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