Show simple item record

dc.contributor.authorBaggott, Rhiannon R
dc.contributor.authorAlfranca, Arantzazu
dc.contributor.authorLópez-Maderuelo, Dolores
dc.contributor.authorMohamed, Tamer M A
dc.contributor.authorEscolano, Amelia
dc.contributor.authorOller, Jorge
dc.contributor.authorOrnes, Beatriz C
dc.contributor.authorKurusamy, Sathishkumar
dc.contributor.authorRowther, Farjana B
dc.contributor.authorBrown, James E
dc.contributor.authorOceandy, Delvac
dc.contributor.authorCartwright, Elizabeth J
dc.contributor.authorWang, Weiguang
dc.contributor.authorGómez-del Arco, Pablo
dc.contributor.authorMartínez-Martínez, Sara
dc.contributor.authorNeyses, Ludwig
dc.contributor.authorRedondo, Juan Miguel
dc.contributor.authorArmesilla, Angel
dc.date.accessioned2018-09-13T09:52:28Z
dc.date.available2018-09-13T09:52:28Z
dc.date.issued2014-08-21
dc.identifier.citationBaggott, R. R. et al. (2014) Plasma membrane calcium ATPase isoform 4 inhibits vascular endothelial growth factor-mediated angiogenesis through interaction with calcineurin, Arteriosclerosis, Thrombosis, and Vascular Biology, 34(10), pp. 2310-2320.
dc.identifier.issn1079-5642
dc.identifier.pmid25147342
dc.identifier.doi10.1161/ATVBAHA.114.304363
dc.identifier.urihttp://hdl.handle.net/2436/621699
dc.description.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.
dc.language.isoen
dc.publisherLippincott
dc.subjectangiogenesis effect
dc.subjectcalcineurin
dc.subjectcalcium
dc.subjectnuclear factors of activated T cells
dc.subjectplasma membrane calcium–transporting ATPase
dc.titlePlasma membrane calcium ATPase isoform 4 inhibits vascular endothelial growth factor-mediated angiogenesis through interaction with calcineurin.
dc.typeJournal article
dc.identifier.journalArteriosclerosis, Thrombosis, and Vascular Biology
dc.date.accepted2014-08-06
rioxxterms.funderUniversity of Wolverhampton
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
rioxxterms.licenseref.startdate2018-09-13
dc.source.journaltitleArteriosclerosis, thrombosis, and vascular biology
dc.source.volume34
dc.source.issue10
dc.source.beginpage2310
dc.source.endpage2320
refterms.dateFOA2020-03-04T12:17:46Z


Files in this item

Thumbnail
Name:
Accepted version Baggott et al ...
Size:
2.600Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

https://creativecommons.org/licenses/by-nc-nd/4.0/
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc-nd/4.0/