Salvia Miltiorrhiza Nanovesicles: A Strategy to Reprogram Myeloid Cells for Atherosclerosis Therapy via Immune Modulation.

Abstract

<p>INTRODUCTION: Research has shown that herbal medicine-derived vesicles act as biological agents and drug carriers. This study explores how Salvia miltiorrhiza nanovesicles alleviate atherosclerosis by regulating myeloid cells and inflammation. METHODS: We prepared SDNVs using high-speed centrifugation and analyzed them with nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and live imaging. Atherosclerosis was studied in ApoE-/- mice using models with bone marrow-derived macrophages (BMDM) and monocyte-derived macrophages (MDM). Macrophages were classified with immunofluorescence staining, and cytokines and inflammatory factors were measured using qRT-PCR and ELISA. Flow cytometry identified bone marrow stem cells, progenitor cells, and blood cell types. RESULTS: SDNVs exhibited characteristics of plant extracellular vesicles and significantly lowered total cholesterol, triglycerides, and LDL levels in atherosclerotic mice. Immunofluorescence staining showed fewer pro-inflammatory (M1) macrophages and more anti-inflammatory (M2) macrophages in arterial plaques. qRT-PCR and ELISA revealed reduced levels of inflammatory markers in the aorta and serum. Flow cytometry showed decreased bone marrow hematopoietic stem cells (Lin- Sca-1+ cKit+), progenitor cells (MPP4), and monocytes and neutrophils in peripheral blood. SDNVs also inhibited M1 polarization and promoted M2 polarization in BMDMs. DISCUSSION: SDNVs exert potent anti-atherosclerotic effects through lipid regulation and immune modulation, thus advancing PDEV-based therapeutic strategies for atherosclerosis. Limitations involve the use of a single ApoE-/- mouse model and unclear underlying mechanisms of cellular SDNV uptake. CONCLUSION: SDNVs demonstrate immune-regulating and anti-inflammatory effects. They effectively enter the body and modulate bone marrow cell, blood cell production, macrophage behavior, and inflammation, thereby slowing the progression of atherosclerosis.</p>