Plasma membrane calcium ATPase isoform 4 inhibits vascular endothelial growth factor-mediated angiogenesis through interaction with calcineurin.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsBaggott, Rhiannon R
Mohamed, Tamer M A
Ornes, Beatriz C
Rowther, Farjana B
Brown, James E
Cartwright, Elizabeth J
Gómez-del Arco, Pablo
Redondo, Juan Miguel
Armesilla, Angel Luis
MetadataShow full item record
AbstractVascular endothelial growth factor (VEGF) has been identified as a crucial regulator of physiological and pathological angiogenesis. Among the intracellular signaling pathways triggered by VEGF, activation of the calcineurin/nuclear factor of activated T cells (NFAT) signaling axis has emerged as a critical mediator of angiogenic processes. We and others previously reported a novel role for the plasma membrane calcium ATPase (PMCA) as an endogenous inhibitor of the calcineurin/NFAT pathway, via interaction with calcineurin, in cardiomyocytes and breast cancer cells. However, the functional significance of the PMCA/calcineurin interaction in endothelial pathophysiology has not been addressed thus far. Using in vitro and in vivo assays, we here demonstrate that the interaction between PMCA4 and calcineurin in VEGF-stimulated endothelial cells leads to downregulation of the calcineurin/NFAT pathway and to a significant reduction in the subsequent expression of the NFAT-dependent, VEGF-activated, proangiogenic genes RCAN1.4 and Cox-2. PMCA4-dependent inhibition of calcineurin signaling translates into a reduction in endothelial cell motility and blood vessel formation that ultimately impairs in vivo angiogenesis by VEGF. Given the importance of the calcineurin/NFAT pathway in the regulation of pathological angiogenesis, targeted modulation of PMCA4 functionality might open novel therapeutic avenues to promote or attenuate new vessel formation in diseases that occur with angiogenesis.
- Selective inhibition of plasma membrane calcium ATPase 4 improves angiogenesis and vascular reperfusion.
- Authors: Kurusamy S, López-Maderuelo D, Little R, Cadagan D, Savage AM, Ihugba JC, Baggott RR, Rowther FB, Martínez-Martínez S, Arco PG, Murcott C, Wang W, Francisco Nistal J, Oceandy D, Neyses L, Wilkinson RN, Cartwright EJ, Redondo JM, Armesilla AL
- Issue date: 2017 Aug
- S100A1 deficiency impairs postischemic angiogenesis via compromised proangiogenic endothelial cell function and nitric oxide synthase regulation.
- Authors: Most P, Lerchenmüller C, Rengo G, Mahlmann A, Ritterhoff J, Rohde D, Goodman C, Busch CJ, Laube F, Heissenberg J, Pleger ST, Weiss N, Katus HA, Koch WJ, Peppel K
- Issue date: 2013 Jan 4
- Down syndrome candidate region 1 isoform 1 mediates angiogenesis through the calcineurin-NFAT pathway.
- Authors: Qin L, Zhao D, Liu X, Nagy JA, Hoang MV, Brown LF, Dvorak HF, Zeng H
- Issue date: 2006 Nov
- Nuclear factor of activated T cells and early growth response-1 cooperate to mediate tissue factor gene induction by vascular endothelial growth factor in endothelial cells.
- Authors: Schabbauer G, Schweighofer B, Mechtcheriakova D, Lucerna M, Binder BR, Hofer E
- Issue date: 2007 Jun
- VEGF stimulates RCAN1.4 expression in endothelial cells via a pathway requiring Ca2+/calcineurin and protein kinase C-delta.
- Authors: Holmes K, Chapman E, See V, Cross MJ
- Issue date: 2010 Jul 6