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- Title
Endocytosis of red blood cell extracellular vesicles by macrophages leads to cytoplasmic heme release and prevents foam cell formation in atherosclerosis.
- Authors
Pham, Thach Tuan; Le, Anh Hong; Dang, Cong Phi; Chong, Suet Yen; Do, Dang Vinh; Peng, Boya; Jayasinghe, Migara Kavishka; Ong, Hong Boon; Hoang, Dong Van; Louise, Roma Anne; Loh, Yuin‐Han; Hou, Han Wei; Wang, Jiong‐Wei; Le, Minh TN
- Abstract
Extracellular vesicles (EVs) can be produced from red blood cells (RBCs) on a large scale and used to deliver therapeutic payloads efficiently. However, not much is known about the native biological properties of RBCEVs. Here, we demonstrate that RBCEVs are primarily taken up by macrophages and monocytes. This uptake is an active process, mediated mainly by endocytosis. Incubation of CD14+ monocytes with RBCEVs induces their differentiation into macrophages with an Mheme‐like phenotype, characterized by upregulation of heme oxygenase‐1 (HO‐1) and the ATP‐binding cassette transporter ABCG1. Moreover, macrophages that take up RBCEVs exhibit a reduction in surface CD86 and decreased secretion of TNF‐α under inflammatory stimulation. The upregulation of HO‐1 is attributed to heme derived from haemoglobin in RBCEVs. Heme is released from internalized RBCEVs in late endosomes and lysosomes via the heme transporter, HRG1. Consequently, RBCEVs exhibit the ability to attenuate foam cell formation from oxidized low‐density lipoproteins (oxLDL)‐treated macrophages in vitro and reduce atherosclerotic lesions in ApoE knockout mice on a high‐fat diet. In summary, our study reveals the uptake mechanism of RBCEVs and their delivery of heme to macrophages, suggesting the potential application of RBCEVs in the treatment of atherosclerosis.
- Subjects
ERYTHROCYTES; FOAM cells; ENDOCYTOSIS; EXTRACELLULAR vesicles; HEME; ATP-binding cassette transporters; ERYTHROCYTE membranes; MONOAMINE transporters
- Publication
Journal of Extracellular Vesicles, 2023, Vol 12, Issue 8, p1
- ISSN
2001-3078
- Publication type
Article
- DOI
10.1002/jev2.12354