Plasma Microvesicles May Contribute to Muscle Damage in the mdx Mouse Model of Duchenne Muscular Dystrophy

Extracellular vesicles (EVs) are cell-derived lipid-bound vesicles divided into apoptotic bodies, microvesicles (MVs), and exosomes based on their biogenesis, release pathway, size, content, and functions. EVs are intercellular mediators that significantly affect muscle diseases such as Duchenne muscular dystrophy (DMD). DMD is a fatal X-linked disorder caused by mutations in the dystrophin gene, leading to muscle degeneration. <i>Mdx</i> mice are the most commonly used model to study the disease, and in this study, we phenotypically characterized plasma MVs from <i>mdx</i> mice by flow cytometry. Furthermore, we assessed the ability of plasma MVs to modulate muscle inflammation, damage, and/or regeneration by intramuscular injection of MVs from <i>mdx</i> mice into <i>mdx</i> or DBA/2 mice as a control. In both mouse lineages, platelets and erythrocytes were the primary sources of MVs, and CD3⁺ CD4⁺ MVs were observed only in <i>mdx</i> mice. We also observed that plasma MVs from <i>mdx</i> mice induced muscle damage in <i>mdx</i> mice but not in DBA/2 mice, while plasma MVs from DBA/2 mice did not induce muscle damage in either mouse lineage. These results indicate that plasma MVs from <i>mdx</i> are potentially pathogenic. However, this condition also depends on the muscular tissue status, which must be responsive due to active inflammatory or regenerative responses.