Pitavastatin-loaded procyanidins self-assembled nanoparticles alleviate advanced atherosclerosis via modulating macrophage efferocytosis and cholesterol efflux.
10.1016/j.apsb.2024.08.006
- Author:
Yizhou WU
1
;
Hongyan ZHOU
2
;
Hao LIU
3
;
Jiayao HU
1
;
Yue SUN
1
;
Wei YAN
4
;
Chunyi TONG
1
;
Ying KONG
3
;
Bin LIU
1
Author Information
1. College of Biology, Hunan University, Changsha 410082, China.
2. Precision Pharmacy & Drug Development Center, Department of Pharmacy, Second Affiliated Hospital, Air Force Medical University, Xi'an 710038, China.
3. Department of Rehabilitation, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
4. Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China.
- Publication Type:Journal Article
- Keywords:
Advanced atherosclerosis;
Efferocytosis;
Macrophage lipophagy;
Pitavastatin;
Procyanidins;
Self-assembled nanoparticles
- From:
Acta Pharmaceutica Sinica B
2025;15(6):3305-3320
- CountryChina
- Language:English
-
Abstract:
Advanced atherosclerosis is the major global cause of death, as featured by the aggregation of apoptotic cells (ACs) in necrotic cores. The defective efferocytosis and dysfunctional cholesterol efflux of macrophages are the main reasons for forming necrotic cores in advanced atherosclerosis. In this study, we constructed self-assembled procyanidins (PC) NPs for loading pitavastatin (Pita). The designed HA@PC@Pita NPs with hyaluronic acid (HA) modification combined the advantages of efferocytosis restoration of Pita and cholesterol efflux enhancement of PC. In vitro assay indicated that HA@PC@Pita NPs could induce M1/M2 repolarization and upregulate ERK5/Mertk expression to restore efferocytosis of macrophages. Simultaneously, HA@PC@Pita NPs notably promoted cholesterol efflux by promoting macrophage lipophagy, a selective autophagy of lipid droplets. In vivo study showed that HA@PC@Pita NPs cleared necrotic core and enhanced plaque stability in the ApoE -/- mice model with advanced atherosclerosis. Taken together, this study demonstrated the potential of HA@PC@Pita NPs for the treatment of advanced atherosclerosis.
