- Bouchareychas, Laura;
- Duong, Phat;
- Covarrubias, Sergio;
- Alsop, Eric;
- Phu, Tuan Anh;
- Chung, Allen;
- Gomes, Michael;
- Wong, David;
- Meechoovet, Bessie;
- Capili, Allyson;
- Yamamoto, Ryo;
- Nakauchi, Hiromitsu;
- McManus, Michael T;
- Carpenter, Susan;
- Van Keuren-Jensen, Kendall;
- Raffai, Robert L
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.