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 journalArticle

4 Citations (Scopus)

Abstract

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
JournalTheranostics
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Jan 1

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Peroxisome Proliferator-Activated Receptors
Optical Imaging
Therapeutic Uses
Macrophages
Inflammation
Foam Cells
Macrophage Activation
Atherosclerotic Plaques
Carotid Arteries
Aorta
Rupture
Atherosclerosis
Peptide Hydrolases
Anti-Inflammatory Agents
Cholesterol
mannose receptor
Lipids

Keywords

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

ASJC Scopus subject areas

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

Cite this

Therapeutic effects of targeted PPARγ activation on inflamed high-risk plaques assessed by serial optical imaging in vivo. / Choi, Jah Yeon; Ryu, Jiheun; Kim, Hyun Jung; Song, Joon Woo; Jeon, Joo Hee; Lee, Dae Hee; Oh, Dong Joo; Gweon, Dae Gab; Oh, Wang Yuhl; Yoo, Hongki; Park, Kyeongsoon; Kim, Jin Won.

In: Theranostics, Vol. 8, No. 1, 01.01.2018, p. 45-60.

Research output: Contribution to journalArticle

Choi, JY, Ryu, J, Kim, HJ, Song, JW, Jeon, JH, Lee, DH, Oh, DJ, Gweon, DG, Oh, WY, Yoo, H, Park, K & Kim, JW 2018, 'Therapeutic effects of targeted PPARγ activation on inflamed high-risk plaques assessed by serial optical imaging in vivo', Theranostics, vol. 8, no. 1, pp. 45-60. https://doi.org/10.7150/thno.20885
Choi, Jah Yeon ; Ryu, Jiheun ; Kim, Hyun Jung ; Song, Joon Woo ; Jeon, Joo Hee ; Lee, Dae Hee ; Oh, Dong Joo ; Gweon, Dae Gab ; Oh, Wang Yuhl ; Yoo, Hongki ; Park, Kyeongsoon ; Kim, Jin Won. / Therapeutic effects of targeted PPARγ activation on inflamed high-risk plaques assessed by serial optical imaging in vivo. In: Theranostics. 2018 ; Vol. 8, No. 1. pp. 45-60.
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AU - Jeon, Joo Hee

AU - Lee, Dae Hee

AU - Oh, Dong Joo

AU - Gweon, Dae Gab

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AU - Yoo, Hongki

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AU - Kim, Jin Won

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