M1-like macrophage-derived exosomes suppress angiogenesis and exacerbate cardiac dysfunction in a myocardial infarction microenvironment

In this study, we investigated the role of M1-like macrophage-derived exosomes in a MI microenvironment. We found that the proinflammatory M1-like-type macrophages released an extensive array of proinflammatory exosomes (M1-Exos) after MI. M1-Exos exerted an anti-angiogenic effect and accelerated MI injury. They also exhibited highly expressed proinflammatory miRNAs, such as miR-155. miR-155 was transferred to endothelial cells (ECs), leading to the inhibition of angiogenesis and cardiac dysfunction by downregulating its novel target genes, including Rac family small GTPase 1 (RAC1), p21 (RAC1)-activated kinase 2 (PAK2), Sirtuin 1 (Sirt1), and protein kinase AMP-activated catalytic subunit alpha 2 (AMPK α2). M1-Exos depressed Sirt1/AMPKα2–endothelial nitric oxide synthase and RAC1–PAK2 signaling pathways by simultaneously targeting the five molecule nodes (genes), reduced the angiogenic ability of ECs, aggravated myocardial injury, and restrained cardiac healing. The elucidation of this mecha nism provides novel insights into the functional significance of M1 macrophages and their derived exosomes on angiogenesis and cardiac repair. This mechanism can be used as a novel potential therapeutic approach for the prevention and treatment of MI.

Source: Basic Research in Cardiology - February 27, 2020 Category: Cardiology Source Type: research