Integrated Proteomic and Transcriptomic Analysis of Adipose Tissue-Derived Small Extracellular Vesicles in Ischemic Stroke.

PURPOSE: Ischemic stroke (IS) is a severe neurological disease with limited treatment options. Subcutaneous adipose tissue-derived small extracellular vesicles (SAT-sEVs), which are readily accessible and abundant, have emerged as promising biomarkers and therapeutic agents in various diseases. The objective of this research is to uncover the roles and regulatory mechanisms of proteins and miRNAs contained within SAT-sEVs in middle cerebral artery occlusion (MCAO) rats, aiming to discover innovative approaches and insights for IS treatment.

EXPERIMENTAL

DESIGN

To evaluate the therapeutic efficacy of SAT-sEVs, we intravenously administered them to MCAO rats and assessed neurological function and cerebral infarction 24 h after SAT-sEVs administration using behavioral scoring and TTC staining. To elucidate the potential mechanisms and ischemia-induced alterations in SAT-sEVs, we conducted integrated transcriptomic and proteomic analyses on vesicles isolated from both MCAO rats (24-h post-ischemia) and normal controls.

RESULTS

SAT-sEVs markedly alleviated neurological impairments and decreased the volume of cerebral infarcts in MCAO rats. Significant alterations were also observed in the miRNAs and proteins within SAT-sEVs following ischemic injury.

CONCLUSIONS AND CLINICAL RELEVANCE: This comprehensive analysis enhances our understanding of SAT-sEVs-mediated protective mechanisms and functional alterations in IS. It establishes a solid experimental basis for the potential clinical use of SAT-sEVs in stroke rehabilitation and other related diseases.