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Therapeutic Effects of Targeted PPAR. Activation on Inflamed High-Risk Plaques Assessed by Serial Optical Imaging In Vivo

Title
Therapeutic Effects of Targeted PPAR. Activation on Inflamed High-Risk Plaques Assessed by Serial Optical Imaging In Vivo
Author
유홍기
Keywords
Macrophage; Targeted; Plaque; PPAR gamma; Lobeglitazone; Serial imaging
Issue Date
2018-01
Publisher
IVYSPRING INT PUBL
Citation
THERANOSTICS, v. 8, no. 1, page. 45-60
Abstract
Rationale: Atherosclerotic plaque is a chronic inflammatory disorder involving lipid accumulation within arterial walls. In particular, macrophages mediate plaque progression and rupture. While PPAR. 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 PPAR. 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 PPAR. 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 LXR alpha, 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 PPAR. pathways within high-risk plaques and effectively reduce both plaque burden and inflammation. This novel targetable PPAR. activation in macrophages could be a promising therapeutic strategy for high-risk plaques.
URI
http://www.thno.org/v08p0045.htmhttps://repository.hanyang.ac.kr/handle/20.500.11754/117242
ISSN
1838-7640
DOI
10.7150/thno.20885
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > ELECTRICAL AND BIOMEDICAL ENGINEERING(전기·생체공학부) > Articles
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