Scientific reports, 2020-02, Vol.10 (1), p.2494-2494, Article 2494
2020
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- Autor(en) / Beteiligte
- Titel
- Ticagrelor Enhances Release of Anti-Hypoxic Cardiac Progenitor Cell-Derived Exosomes Through Increasing Cell Proliferation In Vitro
- Ist Teil von
- Scientific reports, 2020-02, Vol.10 (1), p.2494-2494, Article 2494
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2020
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Despite the widespread clinical use of cardioprotection by long-term direct antagonism of P2Y12 receptor, underlying mechanisms are unclear. Here, we identify how release of pro-survival exosomes from human cardiac-derived mesenchymal progenitor cells (hCPCs) is regulated by clinically relevant dose of ticagrelor (1 μM), an oral selective and reversible non-thienopyridine P2Y inhibitor. Ticagrelor-induced enhancement of exosome levels is related to increased mitotic activity of hCPCs. We show a drug-response threshold above which the effects on hCPCs are lost due to higher dose of ticagrelor and larger adenosine levels. While it is known that pan-Aurora kinase inhibitor halts cell proliferation through dephosphorylation of histone H3 residue Ser10, we demonstrate that it also prevents ticagrelor-induced effects on release of cardiac progenitor cell-derived exosomes delivering anti-apoptotic HSP70. Indeed, sustained pre-treatment of cardiomyocytes with exosomes released from explant-derived hCPCs exposed to low-dose ticagrelor attenuated hypoxia-induced apoptosis through acute phosphorylation of ERK42/44. Our data indicate that ticagrelor can be leveraged to modulate release of anti-hypoxic exosomes from resident hCPCs.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/s41598-020-59225-7Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7016113
- Format
- –
- Schlagworte
- Adenosine, Aged, Animals, Apoptosis, Aurora kinase, Aurora Kinases - metabolism, Cardiomyocytes, Cell growth, Cell Hypoxia, Cell Proliferation, Cells, Cultured, Dephosphorylation, Enzyme inhibitors, Exosomes, Exosomes - drug effects, Exosomes - metabolism, Heart, Histone H3, HSP70 Heat-Shock Proteins - metabolism, Hsp70 protein, Humans, Hypoxia, Kinases, MAP Kinase Signaling System, Mesenchyme, Mice, Myocytes, Cardiac - drug effects, Myocytes, Cardiac - metabolism, Myocytes, Cardiac - physiology, Phosphorylation, Progenitor cells, Purinergic P2Y Receptor Antagonists - pharmacology, Stem cells, Ticagrelor - pharmacology