The TRPC5 channel regulates angiogenesis and promotes recovery from ischemic injury in mice.
angiogenesis
calcium channel
cardiovascular disease
hypoxia
ion channel
ischemia
transient receptor potential channels (TRP channels)
vascular biology
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
04 01 2019
04 01 2019
Historique:
received:
15
08
2018
revised:
06
11
2018
pubmed:
11
11
2018
medline:
10
4
2019
entrez:
11
11
2018
Statut:
ppublish
Résumé
Ischemia-related diseases are a leading cause of death worldwide, and promoting therapeutic angiogenesis is key for effective recovery from hypoxia-ischemia. Given the limited success of angiogenic factors, such as vascular endothelial growth factor, in clinical trials, it is important to find more promising angiogenic targets. Here, using both cell- and tissue-based assays and a mouse model of injury-induced ischemia, we investigated the involvement of the transient receptor potential canonical 5 (TRPC5) ion channel in angiogenesis and the effects of a TRPC5 activator, the Food and Drug Administration-approved drug riluzole, on recovery from ischemic injury. We demonstrate that TRPC5 is involved in endothelial cell sprouting, angiogenesis, and blood perfusion in an oxygen-induced retinopathy model and a hind limb ischemia model. We found a potential regulatory link between nuclear factor of activated T cell isoform c3 and angiopoietin-1 that could provide the mechanistic basis for the angiogenic function of TRPC5. Importantly, treatment with riluzole, which can activate TRPC5 in endothelial cells, improved recovery from ischemia in mice. Our study reveals TRPC5 as a potential angiogenic target and suggests riluzole as a promising drug for managing ischemic diseases.
Identifiants
pubmed: 30413532
pii: S0021-9258(20)36871-X
doi: 10.1074/jbc.RA118.005392
pmc: PMC6322878
pii:
doi:
Substances chimiques
TRPC Cation Channels
0
Trpc5 protein, mouse
0
Riluzole
7LJ087RS6F
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
28-37Informations de copyright
© 2019 Zhu et al.
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