Endocytosis of red blood cell extracellular vesicles by macrophages leads to cytoplasmic heme release and prevents foam cell formation in atherosclerosis.

Autor: Pham TT; Department of Pharmacology, and Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Le AH; Department of Pharmacology, and Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Dang CP; Department of Pharmacology, and Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Chong SY; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Do DV; Department of Pharmacology, and Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Peng B; Department of Pharmacology, and Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Jayasinghe MK; Department of Pharmacology, and Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Ong HB; School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore, Singapore.; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore., Hoang DV; Department of Pharmacology, and Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Louise RA; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Loh YH; A*STAR Institute of Molecular and Cell Biology, Singapore, Singapore.; Department of Biological Sciences, National University of Singapore, Singapore, Singapore., Hou HW; School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore, Singapore.; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore., Wang JW; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Le MT; Department of Pharmacology, and Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; A*STAR Institute of Molecular and Cell Biology, Singapore, Singapore.
Jazyk: angličtina
Zdroj: Journal of extracellular vesicles [J Extracell Vesicles] 2023 Aug; Vol. 12 (8), pp. e12354.
DOI: 10.1002/jev2.12354
Abstrakt: 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.
(© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje