PT  - JOURNAL ARTICLE
AU  - Kurusamy, S
AU  - Baggott, RR
AU  - López-Maderuelo, MD
AU  - Kannappan, V
AU  - Escolano, A
AU  - Oller, J
AU  - Little, R
AU  - Dunmore, SJ
AU  - Oceandy, D
AU  - Cartwright, EJ
AU  - Wang, W
AU  - Neyses, L
AU  - Redondo, JM
AU  - Armesilla, AL
TI  - THE PLASMA MEMBRANE CALCIUM ATPASE 4 SPECIFIC INHIBITOR AURINTRICARBOXYLIC ACID ENHANCES VEGF-INDUCED ANGIOGENESIS
AID  - 10.1136/heartjnl-2014-306916.72
DP  - 2014 Dec 01
TA  - Heart
PG  - A24--A24
VI  - 100
IP  - Suppl 4
4099  - http://heart.bmj.com/content/100/Suppl_4/A24.short
4100  - http://heart.bmj.com/content/100/Suppl_4/A24.full
SO  - Heart2014 Dec 01; 100
AB  - Angiogenesis, the formation of new capillaries from pre-existing ones, is a biological process essential for successful embryonic development, organ growth and tissue repair. Excessive or insufficient growth of blood vessels, due to de-regulation of this process, plays a major role in the pathophysiology of several human diseases. The pro-angiogenic factor Vascular Endothelial Growth Factor (VEGF) has been identified as a crucial regulator of both physiological and pathological angiogenesis. VEGF activates the calcineurin/Nuclear Factor of Activated T-cells (NFAT) signalling pathway which is a critical mediator of angiogenesis. Our group has recently identified a novel role for the plasma membrane calcium ATPase 4 (PMCA4) as a negative regulator of VEGF-dependent angiogenesis. The small molecule Aurintricarboxylic acid (ATA) has been characterised as a selective inhibitor of PMCA4. We hypothesise that ATA-mediated inhibition of PMCA4 in endothelial cells will enhance VEGF-driven angiogenesis. Consistent with this hypothesis, we demonstrate in this work that inhibition of PMCA4 by treatment with ATA increases calcineurin/NFAT activity and the expression of the NFAT-dependent, pro-angiogenic protein RCAN1.4 in VEGF-stimulated HUVEC. Moreover, ATA treatment significantly enhanced endothelial cell migration and tubular morphogenesis in response to VEGF-stimulation. Interestingly, incubation of HUVEC with ATA had no effect on the cell viability or Erk1/2 phosphorylation (activation) status of VEGF-stimulated cells. Our results show a novel role for the PMCA4 specific inhibitor ATA as a stimulator of VEGF-induced angiogenesis. Thus, ATA might lead to the design of new therapeutic strategies to improve blood vessel formation in diseases associated with insufficient angiogenesis.