| 초록 |
While PPARγ agonist is known to have faborable pleiotropic effects on atherogenesis, its clinical application has been very limited due to undesirable systemic effects. Herein we newly developed macrophage mannose receptor (MMR)-targeted biocompatible nanocarrier loaded with lobeglitazone (MMR-Lobe), which is able to specifically activate PPARγ pathways within the inflamed high-risk plaques. MMR-Lobe had a high affinity to macrophage foam cells, and it could efficiently promote cholesterol efflux via LXRα, ABCA1-, 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 systemic effects. Comprehensive analysis of en face aorta by ex vivo imaging and immunostainings well corroborated the in vivo findings. This novel targetable PPARγ activation in macrophages could be a promising therapeutic strategy for high-risk plaques. |
