Pitavastatin-loaded procyanidins self-assembled nanoparticles alleviate advanced atherosclerosis via modulating macrophage efferocytosis and cholesterol efflux
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...
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Elsevier
2025-06-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383524003228 |
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| author | Yizhou Wu Hongyan Zhou Hao Liu Jiayao Hu Yue Sun Wei Yan Chunyi Tong Ying Kong Bin Liu |
| author_facet | Yizhou Wu Hongyan Zhou Hao Liu Jiayao Hu Yue Sun Wei Yan Chunyi Tong Ying Kong Bin Liu |
| author_sort | Yizhou Wu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-640151c79ebe49078eaa0a4ca439fe66 |
| institution | Kabale University |
| issn | 2211-3835 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj-art-640151c79ebe49078eaa0a4ca439fe662025-08-20T03:30:05ZengElsevierActa Pharmaceutica Sinica B2211-38352025-06-011563305332010.1016/j.apsb.2024.08.006Pitavastatin-loaded procyanidins self-assembled nanoparticles alleviate advanced atherosclerosis via modulating macrophage efferocytosis and cholesterol effluxYizhou Wu0Hongyan Zhou1Hao Liu2Jiayao Hu3Yue Sun4Wei Yan5Chunyi Tong6Ying Kong7Bin Liu8College of Biology, Hunan University, Changsha 410082, ChinaPrecision Pharmacy & Drug Development Center, Department of Pharmacy, Second Affiliated Hospital, Air Force Medical University, Xi’an 710038, ChinaDepartment of Rehabilitation, The Second Xiangya Hospital, Central South University, Changsha 410011, ChinaCollege of Biology, Hunan University, Changsha 410082, ChinaCollege of Biology, Hunan University, Changsha 410082, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, ChinaKey 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, ChinaCollege of Biology, Hunan University, Changsha 410082, ChinaDepartment of Rehabilitation, The Second Xiangya Hospital, Central South University, Changsha 410011, China; Corresponding authors.College of Biology, Hunan University, Changsha 410082, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S2211383524003228Advanced atherosclerosisProcyanidinsPitavastatinEfferocytosisMacrophage lipophagySelf-assembled nanoparticles |
| spellingShingle | Yizhou Wu Hongyan Zhou Hao Liu Jiayao Hu Yue Sun Wei Yan Chunyi Tong Ying Kong Bin Liu Pitavastatin-loaded procyanidins self-assembled nanoparticles alleviate advanced atherosclerosis via modulating macrophage efferocytosis and cholesterol efflux Acta Pharmaceutica Sinica B Advanced atherosclerosis Procyanidins Pitavastatin Efferocytosis Macrophage lipophagy Self-assembled nanoparticles |
| title | Pitavastatin-loaded procyanidins self-assembled nanoparticles alleviate advanced atherosclerosis via modulating macrophage efferocytosis and cholesterol efflux |
| title_full | Pitavastatin-loaded procyanidins self-assembled nanoparticles alleviate advanced atherosclerosis via modulating macrophage efferocytosis and cholesterol efflux |
| title_fullStr | Pitavastatin-loaded procyanidins self-assembled nanoparticles alleviate advanced atherosclerosis via modulating macrophage efferocytosis and cholesterol efflux |
| title_full_unstemmed | Pitavastatin-loaded procyanidins self-assembled nanoparticles alleviate advanced atherosclerosis via modulating macrophage efferocytosis and cholesterol efflux |
| title_short | Pitavastatin-loaded procyanidins self-assembled nanoparticles alleviate advanced atherosclerosis via modulating macrophage efferocytosis and cholesterol efflux |
| title_sort | pitavastatin loaded procyanidins self assembled nanoparticles alleviate advanced atherosclerosis via modulating macrophage efferocytosis and cholesterol efflux |
| topic | Advanced atherosclerosis Procyanidins Pitavastatin Efferocytosis Macrophage lipophagy Self-assembled nanoparticles |
| url | http://www.sciencedirect.com/science/article/pii/S2211383524003228 |
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