Theranostics 2018; 8(1):45-60. doi:10.7150/thno.20885 This issue Cite

Research Paper

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

Jah Yeon Choi1,*, Jiheun Ryu2,*, Hyun Jung Kim1,*, Joon Woo Song1, Joo Hee Jeon1, Dae-Hee Lee3, Dong Joo Oh1, Dae-Gab Gweon2, Wang-Yuhl Oh2, Hongki Yoo4,✉, Kyeongsoon Park5,✉, Jin Won Kim1,✉

1. Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea, 152-703
2. Department of Mechanical Engineering, KAIST, Daejeon, Republic of Korea, 305-701
3. Division of Medical Oncology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea, 152-703
4. Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea, 133-791
5. Department of Systems Biotechnology, College of Biotechnology and Natural Resources, Chung-Ang University, Anseong-si, Gyeonggi-do, Republic of Korea, 17546
*JYC, JR, HJK contributed equally to this work.

Citation:
Choi JY, Ryu J, Kim HJ, Song JW, Jeon JH, Lee DH, Oh DJ, Gweon DG, Oh WY, Yoo H, Park K, Kim JW. Therapeutic Effects of Targeted PPARɣ Activation on Inflamed High-Risk Plaques Assessed by Serial Optical Imaging In Vivo. Theranostics 2018; 8(1):45-60. doi:10.7150/thno.20885. https://www.thno.org/v08p0045.htm
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Abstract

Graphic 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.

Keywords: Macrophage, Targeted, Plaque, PPARγ, Lobeglitazone, Serial imaging


Citation styles

APA
Choi, J.Y., Ryu, J., Kim, H.J., Song, J.W., Jeon, J.H., Lee, D.H., Oh, D.J., Gweon, D.G., Oh, W.Y., Yoo, H., Park, K., Kim, J.W. (2018). Therapeutic Effects of Targeted PPARɣ Activation on Inflamed High-Risk Plaques Assessed by Serial Optical Imaging In Vivo. Theranostics, 8(1), 45-60. https://doi.org/10.7150/thno.20885.

ACS
Choi, J.Y.; Ryu, J.; Kim, H.J.; Song, J.W.; Jeon, J.H.; Lee, D.H.; Oh, D.J.; Gweon, D.G.; Oh, W.Y.; Yoo, H.; Park, K.; Kim, J.W. Therapeutic Effects of Targeted PPARɣ Activation on Inflamed High-Risk Plaques Assessed by Serial Optical Imaging In Vivo. Theranostics 2018, 8 (1), 45-60. DOI: 10.7150/thno.20885.

NLM
Choi JY, Ryu J, Kim HJ, Song JW, Jeon JH, Lee DH, Oh DJ, Gweon DG, Oh WY, Yoo H, Park K, Kim JW. Therapeutic Effects of Targeted PPARɣ Activation on Inflamed High-Risk Plaques Assessed by Serial Optical Imaging In Vivo. Theranostics 2018; 8(1):45-60. doi:10.7150/thno.20885. https://www.thno.org/v08p0045.htm

CSE
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 PPARɣ Activation on Inflamed High-Risk Plaques Assessed by Serial Optical Imaging In Vivo. Theranostics. 8(1):45-60.

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