Autophagy Induced by a Novel Triazol Derivative Promotes Angiogenesis Through Decreasing Interferon-Inducible Protein 10 Level in Vascular Endothelial Cells.
J Cardiovasc Pharmacol
; 78(1): e136-e146, 2021 07 01.
Article
en En
| MEDLINE
| ID: mdl-34009854
ABSTRACT
ABSTRACT Autophagy plays an important role in angiogenesis, whereas the mechanisms of vascular endothelial cell (VEC) autophagy associated with angiogenesis remain unclear. In this study, we identified a novel triazol derivative (JL025) that significantly promoted angiogenesis both in vitro and in vivo. Moreover, JL025 had no effects on cell proliferation but dramatically increased the autophagy level of VEC. The suppression of autophagy inhibited JL025-induced angiogenesis in vitro and in vivo, suggesting that JL025-induced angiogenesis was dependent on the enhanced autophagy. Mechanistic studies indicated that JL025-induced VEC autophagy was related to the Protein Kinase B/mTOR signaling pathway. Meanwhile, JL025 decreased the antiangiogenic chemokine interferon-inducible protein 10 (IP10) protein level in human VECs. Importantly, the suppression of autophagy inhibited JL025-induced decrease of IP10 protein level, indicating that autophagy mediated the degradation of IP10. Taken together, our findings provide new insights into the relationship of VEC autophagy with angiogenesis, and JL025 may have a therapeutic potential in related diseases.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Autofagia
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Triazoles
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Neovascularización Fisiológica
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Inductores de la Angiogénesis
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Quimiocina CXCL10
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Células Endoteliales de la Vena Umbilical Humana
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Cardiovasc Pharmacol
Año:
2021
Tipo del documento:
Article