Small Extracellular Vesicles from Young Healthy Human Plasma Inhibit Cardiac Fibrosis After Myocardial Infarction via miR-664a-3p Targeting SMAD4

作者：Weiwei Wang, Ying Li, Cheng Zhang, Haoyang Zhou, Chunyu Li, Rong Cheng, Xufeng Chen, Yanan Pu, Yan Chen · 发表于：International Journal of Nanomedicine · 年份：2025 · DOI：10.2147/ijn.s488368 · 被引用次数：9 · 研究领域：Cardiac Fibrosis and Remodeling、Extracellular vesicles in disease、Tissue Engineering and Regenerative Medicine

Purpose: Cardiac fibrosis, a key contributor to ventricular pathologic remodeling and heart failure, currently lacks effective therapeutic approaches. Patients and Methods: Small extracellular vesicles from young healthy human plasma (Young-sEVs) were characterized via protein marker, transmission electron microscopy, and nanoparticle tracking analysis, then applied in cellular models and mouse models of cardiac fibrosis. Western blotting and qRT-PCR were used to identify protective signaling pathways in cardiac fibroblasts (CFs). Results: Young-sEVs significantly inhibited cardiac fibrosis and subsequent cardiac dysfunction post-myocardial infarction (MI) in mice. The main findings included that echocardiographic assessments four weeks post-MI indicated that Young-sEVs improved left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), and reduced left ventricular internal diameter in diastole (LVIDd) and systole (LVIDs). Treatment with Young-sEVs also decreased Masson-positive fibroblast areas and collagen synthesis in cardiac tissue. However, sEVs from the old control group did not achieve the above effect. Consistent with in vivo results, Young-sEVs could also inhibit the proliferation, migration, and collagen synthesis of CFs in the TGF-β1-induced cellular fibrosis model. High-throughput microRNA (miRNA) sequencing and qRT-PCR analysis revealed that miR-664a-3p was abundant in Young-sEVs. The high expression of miR-664a-3p significantly inhibited the pro...