Loading...
Plasma membrane calcium ATPase isoform 4 inhibits vascular endothelial growth factor-mediated angiogenesis through interaction with calcineurin.
Baggott, Rhiannon R Alfranca, Arantzazu López-Maderuelo, Dolores Mohamed, Tamer M A Escolano, Amelia Oller, Jorge Ornes, Beatriz C Kurusamy, Sathishkumar Rowther, Farjana B Brown, James E
Baggott, Rhiannon R
Alfranca, Arantzazu
López-Maderuelo, Dolores
Mohamed, Tamer M A
Escolano, Amelia
Oller, Jorge
Ornes, Beatriz C
Kurusamy, Sathishkumar
Rowther, Farjana B
Brown, James E
Authors
Baggott, Rhiannon R
Alfranca, Arantzazu
López-Maderuelo, Dolores
Mohamed, Tamer M A
Escolano, Amelia
Oller, Jorge
Ornes, Beatriz C
Kurusamy, Sathishkumar
Rowther, Farjana B
Brown, James E
Oceandy, Delvac
Cartwright, Elizabeth J
Wang, Weiguang
Gómez-del Arco, Pablo
MartÃnez-MartÃnez, Sara
Neyses, Ludwig
Redondo, Juan Miguel
Armesilla, Angel
Alfranca, Arantzazu
López-Maderuelo, Dolores
Mohamed, Tamer M A
Escolano, Amelia
Oller, Jorge
Ornes, Beatriz C
Kurusamy, Sathishkumar
Rowther, Farjana B
Brown, James E
Oceandy, Delvac
Cartwright, Elizabeth J
Wang, Weiguang
Gómez-del Arco, Pablo
MartÃnez-MartÃnez, Sara
Neyses, Ludwig
Redondo, Juan Miguel
Armesilla, Angel
Editors
Other contributors
Affiliation
Epub Date
Issue Date
2014-08-21
Submitted date
Alternative
Abstract
Vascular 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.
Citation
Baggott, 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.
Publisher
Research Unit
PubMed ID
25147342
PubMed Central ID
Embedded videos
Additional Links
Type
Journal article
Language
en
Description
Series/Report no.
ISSN
1079-5642