Ceramide 1-Phosphate Protects Endothelial Colony–Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo
Autor: | Virginie Mignon, Soledad Negrotto, Blandine Dizier, Mirta Schattner, Hebe Agustina Mena, Paula Romina Zubiry, Fernanda Parborell, Catherine Boisson-Vidal |
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Přispěvatelé: | Laboratory of Experimental Thrombosis [Buenos Aires, Argentina] (IMEX), National Academy of Medicine-Institute of Experimental Medicine (IMEX), Thrombose : Épidémiologie, Physiopathologie et Thérapeutiques Innovantes (UMR_S 765), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Optimisation Thérapeutique en Neuropsychopharmacologie (VariaPsy - U1144), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Innovations thérapeutiques en hémostase (IThEM - U1140), Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5) |
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Ceramide CIENCIAS MÉDICAS Y DE LA SALUD Angiogenesis CERMIDE 1 PHOSPHATE Neovascularization Physiologic purl.org/becyt/ford/3.5 [https] Apoptosis [SDV.BC]Life Sciences [q-bio]/Cellular Biology 030204 cardiovascular system & hematology Ceramides Sensitivity and Specificity Mice 03 medical and health sciences chemistry.chemical_compound PROANGIOGENIC 0302 clinical medicine Vasculogenesis Cell Movement In vivo Ischemia Morphogenesis Animals Humans Regeneration Progenitor cell Cells Cultured Cell Proliferation endothelial progenitor cells Regeneration (biology) Cell Differentiation Sphingolipid Otras Ciencias Médicas 3. Good health Cell biology Disease Models Animal 030104 developmental biology chemistry VASCULOGENESIS purl.org/becyt/ford/3 [https] ENDOTHELIAL COLONY FORMING CELLS Cell transplantation Cardiology and Cardiovascular Medicine |
Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2019, 39 (10), ⟨10.1161/ATVBAHA.119.312766⟩ CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
ISSN: | 1079-5642 1524-4636 |
Popis: | Objective: Ceramide 1-phosphate (C1P) is a bioactive sphingolipid highly augmented in damaged tissues. Because of its abilities to stimulate migration of murine bone marrow–derived progenitor cells, it has been suggested that C1P might be involved in tissue regeneration. In the present study, we aimed to investigate whether C1P regulates survival and angiogenic activity of human progenitor cells with great therapeutic potential in regenerative medicine such as endothelial colony–orming cells (ECFCs). Approach and Results: C1P protected ECFC from TNFα (tumor necrosis factor-α)-induced and monosodium urate crystal–induced death and acted as a potent chemoattractant factor through the activation of ERK1/2 (extracellular signal-regulated kinases 1 and 2) and AKT pathways. C1P treatment enhanced ECFC adhesion to collagen type I, an effect that was prevented by β1 integrin blockade, and to mature endothelial cells, which was mediated by the E-selectin/CD44 axis. ECFC proliferation and cord-like structure formation were also increased by C1P, as well as vascularization of gel plug implants loaded or not with ECFC. In a murine model of hindlimb ischemia, local administration of C1P alone promoted blood perfusion and reduced necrosis in the ischemic muscle. Additionally, the beneficial effects of ECFC infusion after ischemia were amplified by C1P pretreatment, resulting in a further and significant enhancement of leg reperfusion and muscle repair. Conclusions: Our findings suggest that C1P may have therapeutic relevance in ischemic disorders, improving tissue repair by itself, or priming ECFC angiogenic responses such as chemotaxis, adhesion, proliferation, and tubule formation, which result in a better outcome of ECFC-based therapy. Fil: Mena, Hebe Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Zubiry, Paula Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Dizier, Blandine. Universite de Paris; Francia. Inserm; Francia Fil: Mignon, Virginie. Inserm; Francia. Universite de Paris; Francia Fil: Parborell, Maria Fernanda Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Boisson Vidal, Catherine. Inserm; Francia. Universite de Paris; Francia Fil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina |
Databáze: | OpenAIRE |
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