Macrophage Exosomes Resolve Atherosclerosis by Regulating Hematopoiesis and Inflammation via MicroRNA Cargo.

Cell Reports
Laura BouchareychasRobert L Raffai

Abstract

Developing strategies that promote the resolution of vascular inflammation and atherosclerosis remains a major therapeutic challenge. Here, we show that exosomes produced by naive bone marrow-derived macrophages (BMDM-exo) contain anti-inflammatory microRNA-99a/146b/378a that are further increased in exosomes produced by BMDM polarized with IL-4 (BMDM-IL-4-exo). These exosomal microRNAs suppress inflammation by targeting NF-κB and TNF-α signaling and foster M2 polarization in recipient macrophages. Repeated infusions of BMDM-IL-4-exo into Apoe-/- mice fed a Western diet reduce excessive hematopoiesis in the bone marrow and thereby the number of myeloid cells in the circulation and macrophages in aortic root lesions. This also leads to a reduction in necrotic lesion areas that collectively stabilize atheroma. Thus, BMDM-IL-4-exo may represent a useful therapeutic approach for atherosclerosis and other inflammatory disorders by targeting NF-κB and TNF-α via microRNA cargo delivery.

Citations

Nov 25, 2020·Wiley Interdisciplinary Reviews. RNA·Joseph Eniafe, Shuai Jiang
Jan 24, 2021·Cardiovascular Research·Luke B RobertsGraham M Lord
Feb 13, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Paulina Pei Suu TanYuh-Fen Pung
Apr 27, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Jiachuan LiuRuiqiang Hang
May 1, 2021·International Journal of Molecular Sciences·Yin LiangKen Takahashi
Jun 4, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Laura R Goldberg
May 20, 2021·Mediators of Inflammation·Pingping WangZengfang Wang
Jun 5, 2021·Frontiers in Pharmacology·Lalitha Sarad Yamini NanduriChandan Guha
Jun 5, 2021·The FEBS Journal·Kaylyn M BauerRyan M O'Connell
Jul 1, 2021·Cell & Bioscience·Mei ZhangXin-Hua Liang
Jul 27, 2021·Frontiers in Cardiovascular Medicine·Zhu Yuan, Weiqiang Huang
Aug 26, 2021·Journal of Extracellular Vesicles·Amin ZakeriPeter Nejsum
Aug 31, 2021·Frontiers in Endocrinology·Anqi ChenYanan Li

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