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

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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Bouchareychas L,Duong P,Covarrubias S,Alsop E,Phu TA,Chung A,Gomes M,Wong D,Meechoovet B,Capili A,Yamamoto R,Nakauchi H,McManus MT,Carpenter S,Van Keuren-Jensen K,Raffai RL

doi

10.1016/j.celrep.2020.107881

subject

Has Abstract

pub_date

2020-07-14 00:00:00

pages

107881

issue

2

issn

2211-1247

pii

S2211-1247(20)30862-7

journal_volume

32

pub_type

杂志文章

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