Abstract
Atherosclerosis has been regarded as a major contributor to cardiovascular disease. The role of extracellular vesicles (EVs) in the treatment of atherosclerosis has been increasingly reported. In this study, we set out to investigate the effect of macrophages-derived EVs (M-EVs) containing miR-19b-3p in the progression of atherosclerosis, with the involvement of JAZF1. Following isolation of EVs from macrophages, the M-EVs were induced with ox-low density lipoprotein (LDL) (ox-LDL-M-EVs), and co-cultured with vascular smooth muscle cells (VSMCs). RT-qPCR and western blot assay were performed to determine the expression of miR-19b-3p and JAZF1 in M-EVs and in VSMCs. Lentiviral infection was used to overexpress or knock down miR-19b-3p. EdU staining and scratch test were conducted to examine VSMC proliferation and migration. Dual-luciferase gene reporter assay was performed to examine the relationship between miR-19b-3p and JAZF1. In order to explore the role of ox-LDL-M-EVs carrying miR-19b-3p in atherosclerotic lesions in vivo, a mouse model of atherosclerosis was established through high-fat diet induction. M-EVs were internalized by VSMCs. VSMC migration and proliferation were promoted by ox-LDL-M-EVs. miR-19b-3p displayed upregulation in ox-LDL-M-EVs. miR-19b-3p was transferred by M-EVs into VSMCs, thereby promoting VSMC migration and proliferation. mir-19b-3p targeted JAZF1 to decrease its expression in VSMCs. Atherosclerosis lesions were aggravated by ox-LDL-M-EVs carrying miR-19b-3p in ApoE-/- mice. Collectively, this study demonstrates that M-EVs containing miR-19b-3p accelerate migration and promotion of VSMCs through targeting JAZF1, which promotes the development of atherosclerosis.