Therapeutic effects of platelet-derived extracellular vesicles on viral myocarditis correlate with biomolecular content
IntroductionExtracellular 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...
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2025-01-01
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| author | Danielle J. Beetler Danielle J. Beetler Danielle J. Beetler Presley Giresi Damian N. Di Florio Damian N. Di Florio Damian N. Di Florio Jessica J. Fliess Elizabeth J. McCabe Molly M. Watkins Molly M. Watkins Molly M. Watkins Vivian Xu Matthew E. Auda Katelyn A. Bruno Katelyn A. Bruno Emily R. Whelan Emily R. Whelan Emily R. Whelan Stephen P. C. Kocsis Brandy H. Edenfield Sierra A. Walker Sierra A. Walker Sierra A. Walker Logan P. Macomb Kevin C. Keegan Angita Jain Angita Jain Angita Jain Andrea C. Morales-Lara Isha Chekuri Anneliese R. Hill Houssam Farres Joy Wolfram Joy Wolfram Atta Behfar Atta Behfar Paul G. Stalboerger Andre Terzic Andre Terzic Leslie T. Cooper DeLisa Fairweather DeLisa Fairweather DeLisa Fairweather |
| author_facet | Danielle J. Beetler Danielle J. Beetler Danielle J. Beetler Presley Giresi Damian N. Di Florio Damian N. Di Florio Damian N. Di Florio Jessica J. Fliess Elizabeth J. McCabe Molly M. Watkins Molly M. Watkins Molly M. Watkins Vivian Xu Matthew E. Auda Katelyn A. Bruno Katelyn A. Bruno Emily R. Whelan Emily R. Whelan Emily R. Whelan Stephen P. C. Kocsis Brandy H. Edenfield Sierra A. Walker Sierra A. Walker Sierra A. Walker Logan P. Macomb Kevin C. Keegan Angita Jain Angita Jain Angita Jain Andrea C. Morales-Lara Isha Chekuri Anneliese R. Hill Houssam Farres Joy Wolfram Joy Wolfram Atta Behfar Atta Behfar Paul G. Stalboerger Andre Terzic Andre Terzic Leslie T. Cooper DeLisa Fairweather DeLisa Fairweather DeLisa Fairweather |
| author_sort | Danielle J. Beetler |
| collection | DOAJ |
| description | IntroductionExtracellular 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.MethodsPEV, 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.ResultsWe 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.DiscussionThese differences in EV content corresponded to the differing anti-inflammatory effects of the two types of EVs on viral myocarditis. |
| format | Article |
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| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-d60bd9a9ef36471c85866e8fa3cdfebf2025-01-06T06:59:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14689691468969Therapeutic effects of platelet-derived extracellular vesicles on viral myocarditis correlate with biomolecular contentDanielle J. Beetler0Danielle J. Beetler1Danielle J. Beetler2Presley Giresi3Damian N. Di Florio4Damian N. Di Florio5Damian N. Di Florio6Jessica J. Fliess7Elizabeth J. McCabe8Molly M. Watkins9Molly M. Watkins10Molly M. Watkins11Vivian Xu12Matthew E. Auda13Katelyn A. Bruno14Katelyn A. Bruno15Emily R. Whelan16Emily R. Whelan17Emily R. Whelan18Stephen P. C. Kocsis19Brandy H. Edenfield20Sierra A. Walker21Sierra A. Walker22Sierra A. Walker23Logan P. Macomb24Kevin C. Keegan25Angita Jain26Angita Jain27Angita Jain28Andrea C. Morales-Lara29Isha Chekuri30Anneliese R. Hill31Houssam Farres32Joy Wolfram33Joy Wolfram34Atta Behfar35Atta Behfar36Paul G. Stalboerger37Andre Terzic38Andre Terzic39Leslie T. Cooper40DeLisa Fairweather41DeLisa Fairweather42DeLisa Fairweather43Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesCenter for Clinical and Translational Science, Mayo Clinic, Rochester, MN, United StatesMayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesCenter for Clinical and Translational Science, Mayo Clinic, Rochester, MN, United StatesMayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesCenter for Clinical and Translational Science, Mayo Clinic, Rochester, MN, United StatesMayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDivision of Cardiovascular Medicine, University of Florida, Gainesville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesCenter for Clinical and Translational Science, Mayo Clinic, Rochester, MN, United StatesMayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cancer Biology, Mayo Clinic, Jacksonville, FL, United StatesMayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, United StatesCenter for Systems Biology, Massachusetts General Hospital, Boston, MA, United StatesDepartment of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesCenter for Clinical and Translational Science, Mayo Clinic, Rochester, MN, United StatesMayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Vascular Surgery, Mayo Clinic, Jacksonville, FL, United StatesSchool of Chemical Engineering, The University of Queensland, Brisbane, QLD, Australia0Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, AustraliaDepartment of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN, United States1Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative Medicine, Rochester, MN, United States1Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative Medicine, Rochester, MN, United States1Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative Medicine, Rochester, MN, United States2Department of Clinical Genomics, Mayo Clinic, Rochester, MN, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, United StatesCenter for Clinical and Translational Science, Mayo Clinic, Rochester, MN, United States3Department of Immunology, Mayo Clinic, Jacksonville, FL, United StatesIntroductionExtracellular 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.MethodsPEV, 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.ResultsWe 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.DiscussionThese differences in EV content corresponded to the differing anti-inflammatory effects of the two types of EVs on viral myocarditis.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1468969/fullcoxsackievirus B3innate immunitycomplementTLR4sex differencesmicroRNA |
| spellingShingle | Danielle J. Beetler Danielle J. Beetler Danielle J. Beetler Presley Giresi Damian N. Di Florio Damian N. Di Florio Damian N. Di Florio Jessica J. Fliess Elizabeth J. McCabe Molly M. Watkins Molly M. Watkins Molly M. Watkins Vivian Xu Matthew E. Auda Katelyn A. Bruno Katelyn A. Bruno Emily R. Whelan Emily R. Whelan Emily R. Whelan Stephen P. C. Kocsis Brandy H. Edenfield Sierra A. Walker Sierra A. Walker Sierra A. Walker Logan P. Macomb Kevin C. Keegan Angita Jain Angita Jain Angita Jain Andrea C. Morales-Lara Isha Chekuri Anneliese R. Hill Houssam Farres Joy Wolfram Joy Wolfram Atta Behfar Atta Behfar Paul G. Stalboerger Andre Terzic Andre Terzic Leslie T. Cooper DeLisa Fairweather DeLisa Fairweather DeLisa Fairweather Therapeutic effects of platelet-derived extracellular vesicles on viral myocarditis correlate with biomolecular content Frontiers in Immunology coxsackievirus B3 innate immunity complement TLR4 sex differences microRNA |
| title | Therapeutic effects of platelet-derived extracellular vesicles on viral myocarditis correlate with biomolecular content |
| title_full | Therapeutic effects of platelet-derived extracellular vesicles on viral myocarditis correlate with biomolecular content |
| title_fullStr | Therapeutic effects of platelet-derived extracellular vesicles on viral myocarditis correlate with biomolecular content |
| title_full_unstemmed | Therapeutic effects of platelet-derived extracellular vesicles on viral myocarditis correlate with biomolecular content |
| title_short | Therapeutic effects of platelet-derived extracellular vesicles on viral myocarditis correlate with biomolecular content |
| title_sort | therapeutic effects of platelet derived extracellular vesicles on viral myocarditis correlate with biomolecular content |
| topic | coxsackievirus B3 innate immunity complement TLR4 sex differences microRNA |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1468969/full |
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