bioRxiv : the preprint server for biology · 2026
Extracellular Vesicles Mediate Activation and Trafficking of Splenic Immune Cells to the Heart Post-Myocardial Infarction.
СтатьяПрепринтНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Fatima Kaneez, Angelotti Austin, Kumar Vinay, Chollangi Vishnu, Aziz Wafa, Dasari Siddarth, Bianchini Emily N, Wang Joseph, Asalla Suman, Singh Harpreet, Prabhu Sumanth D, Bansal Shyam S
Аннотация
BACKGROUND: Myocardial infarction (MI) triggers splenic immune cell trafficking to the heart. Vehicles that carry these signals and mediate this crosstalk are unknown.
HYPOTHESIS: We hypothesize that extracellular vesicles (EVs) released post-MI mediate splenic immune trafficking to the heart.
METHODS: Mice were treated daily with an EV biogenesis inhibitor (GW4869) or vehicle. Splenic/cardiac immune cells were assessed at 3d while survival, cardiac function, hypertrophy, and fibrosis were evaluated at 8w post-MI. Plasma EVs from 1d MI mice or from the hearts that underwent MI/sham in a Langendorff system induced splenic immune trafficking to the heart within 3d and systolic dysfunction at 8w in naïve mice.
RESULTS: GW4869 i) inhibited splenic regression, ii) increased splenic retention of neutrophils, monocytes, dendritic cells (DCs), and CD4+ T-cells, iii) decreased cardiac gene expression of proinflammatory cytokines/chemokines, and iv) decreased trafficking of immune cells to the hearts at 3d post-MI, and iii) improved systolic function and attenuated hypertrophy at 8w post-MI. MI EVs accumulated in the spleen and promoted egress of matured splenic immune cells upon administration to naïve mice. Cardiac pro-inflammatory cytokines/chemokines expression and CCR2+MHC-IIhi infiltrating macrophages, CD11c+ DCs, and CD4+ and CD4+TNFα+ T-cell levels were also increased in naïve mice at 3d post-injection. Importantly, transfer of MI EVs for 2 days induced systolic dysfunction, cellular hypertrophy, and fibrosis in naïve mice at 8 w post-injection. DCs process MI EVs for T-cells activation.
CONCLUSIONS: EVs mobilize splenic immune cells to the heart post-MI and their inhibition can subdue inflammatory tissue-damage to promote healing post-MI.
HYPOTHESIS: We hypothesize that extracellular vesicles (EVs) released post-MI mediate splenic immune trafficking to the heart.
METHODS: Mice were treated daily with an EV biogenesis inhibitor (GW4869) or vehicle. Splenic/cardiac immune cells were assessed at 3d while survival, cardiac function, hypertrophy, and fibrosis were evaluated at 8w post-MI. Plasma EVs from 1d MI mice or from the hearts that underwent MI/sham in a Langendorff system induced splenic immune trafficking to the heart within 3d and systolic dysfunction at 8w in naïve mice.
RESULTS: GW4869 i) inhibited splenic regression, ii) increased splenic retention of neutrophils, monocytes, dendritic cells (DCs), and CD4+ T-cells, iii) decreased cardiac gene expression of proinflammatory cytokines/chemokines, and iv) decreased trafficking of immune cells to the hearts at 3d post-MI, and iii) improved systolic function and attenuated hypertrophy at 8w post-MI. MI EVs accumulated in the spleen and promoted egress of matured splenic immune cells upon administration to naïve mice. Cardiac pro-inflammatory cytokines/chemokines expression and CCR2+MHC-IIhi infiltrating macrophages, CD11c+ DCs, and CD4+ and CD4+TNFα+ T-cell levels were also increased in naïve mice at 3d post-injection. Importantly, transfer of MI EVs for 2 days induced systolic dysfunction, cellular hypertrophy, and fibrosis in naïve mice at 8 w post-injection. DCs process MI EVs for T-cells activation.
CONCLUSIONS: EVs mobilize splenic immune cells to the heart post-MI and their inhibition can subdue inflammatory tissue-damage to promote healing post-MI.