Therapeutic effects of platelet-derived extracellular vesicles on viral myocarditis correlate with biomolecular content
Year: 2025
Type: article
Abstract: Introduction: Extracellular vesicles (EVs) can potently inhibit inflammation yet there is a lack of understanding about the impact of donor characteristics on the efficacy of EVs. The goal of this study was to determine whether the sex and age of donor platelet-derived EVs (PEV) affected their ability to inhibit viral myocarditis. Methods: PEV, isolated from men and women of all ages, was compared to PEV obtained from women under 50 years of age, which we termed premenopausal PEV (pmPEV). Because of the protective effect of estrogen against myocardial inflammation, we hypothesized that pmPEV would be more effective than PEV at inhibiting myocarditis. We injected PEV, pmPEV, or vehicle control in a mouse model of viral myocarditis and examined histology, gene expression, protein profiles, and performed proteome and microRNA (miR) sequencing of EVs. Results: We found that both PEV and pmPEV significantly inhibited myocarditis; however, PEV was more effective, which was confirmed by a greater reduction of inflammatory cells and proinflammatory and profibrotic markers determined using gene expression and immunohistochemistry. Proteome and miR sequencing of EVs revealed that PEV miRs specifically targeted antiviral, Toll-like receptor (TLR)4, and inflammasome pathways known to contribute to myocarditis while pmPEV contained general immunoregulatory miRs. Discussion: These differences in EV content corresponded to the differing anti-inflammatory effects of the two types of EVs on viral myocarditis.
Source: Frontiers in Immunology
Authors: Danielle J. Beetler, Presley Giresi, Damian N. Di Florio, Jessica J. Fliess, Elizabeth J. McCabe, Molly M. Watkins, Vivian Xu, Matthew E. Auda, Katelyn A. Bruno, Emily R. Whelan, Stephen P. C. Kocsis, Brandy H. Edenfield, Sierra A. Walker, Logan P. Macomb, Kevin C. Keegan, Angita Jain, Andrea C. Morales-Lara, Isha Chekuri, Anneliese R. Hill, Houssam Farres, Joy Wolfram, Atta Behfar, Paul G. Stalboerger, Andre Terzic, Leslie T. Cooper, DeLisa Fairweather
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
Awards: Sex differences in novel viral myocarditis therapeutic: adipose-derived stem cell secretome, G2383559136, G2976003695, Novel premenopausal platelet-derived EV therapy for myocarditis/DCM, Role of viral mitophagosomes in driving sex differences in myocarditis, G4238089559, G4254895577, G4334670800, G4379907012, G5027606411, Vitamin D Binding Protein (DBP) in Innate Immune Cell Response in Viral Myocarditis, G5328434511, G5493285022, Adipose-derived biogenic nanoparticles for treatment of myocarditis/DCM(MPDPI), G7051688960, Sex differences in exercise-induced mitochondrial function during viral myocarditis, G8721080112, G9000121016, Mayo Clinic Center for Clinical and Translational Science (CCaTS), Elucidating the innate and adaptive immune mechanism differences during viral myocarditis between pediatric and adult populations: role of sex, age and hormone status, Role of mitochondrial extracellular vesicles in CVB3 myocarditis by sex
OpenAlex ID: W4406083295