Therapeutic Potential of Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicles in Atherosclerotic Stenosis...

Atherosclerotic stenosis is a progressive vascular disease characterized by vascular narrowing. Bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) have been reported to alleviate endothelial cell dysfunction.

Here, we investigated the therapeutic potential of BMSC-EVs in a rabbit model of diabetic atherosclerotic stenosis and in a high-glucose-induced human umbilical vein endothelial cell (HUVEC) injury model.

Histological analysis confirmed the successful establishment of the animal model. Treatment with BMSC-EVs effectively reduced intimal thickening and lipid accumulation, attenuated collagen deposition, reduced smooth muscle cell proliferation, and alleviated macrophage infiltration. Additionally, BMSC-EVs treatment decreased the expression of pro-inflammatory cytokines and improved serum lipid profiles. The HUVEC injury model recapitulates the key features of endothelial dysfunction, including decreased cell viability, increased apoptosis, oxidative stress, and proinflammatory cytokine expression. Treatment with BMSC-EVs alleviated these effects by enhancing cell viability, suppressing apoptosis, reducing oxidative stress, and lowering pro-inflammatory cytokine expression. Mechanistically, BMSC-EVs inhibited the expression of apoptotic markers, including Bax and Cleaved Caspase 3, while enhancing the phosphorylation of heat shock protein 27 (HSP27), a cytoprotective molecule, and its upstream activator P38. HSP27 knockdown reversed the anti-apoptotic and antioxidant effects of BMSC-EVs, highlighting the crucial role of HSP27 in mediating these effects.

Our findings suggest that BMSC-EVs hold promise as a therapeutic intervention for vascular endothelial injury associated with atherosclerosis and diabetes mellitus. Targeting HSP27 may be a potential strategy to enhance the therapeutic efficacy of BMSC-EVs in endothelial dysfunction.