Vascular endothelial growth factor activates nuclear factor of activated T cells in human endothelial cells: a role for tissue factor gene expression.
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
AuthorsArmesilla, Angel Luis
Gómez del Arco, Pablo
Redondo, Juan Miguel
MetadataShow full item record
AbstractVascular endothelial growth factor (VEGF) is a potent angiogenic inducer that stimulates the expression of tissue factor (TF), the major cellular initiator of blood coagulation. Here we show that signaling triggered by VEGF induced DNA-binding and transcriptional activities of nuclear factor of activated T cells (NFAT) and AP-1 in human umbilical vein endothelial cells (HUVECs). VEGF also induced TF mRNA expression and gene promoter activation by a cyclosporin A (CsA)-sensitive mechanism. As in lymphoid cells, NFAT was dephosphorylated and translocated to the nucleus upon activation of HUVECs, and these processes were blocked by CsA. NFAT was involved in the VEGF-mediated TF promoter activation as evidenced by cotransfection experiments with a dominant negative version of NFAT and site-directed mutagenesis of a newly identified NFAT site within the TF promoter that overlaps with a previously identified kappaB-like site. Strikingly, this site bound exclusively NFAT not only from nuclear extracts of HUVECs activated by VEGF, a stimulus that failed to induce NF-kappaB-binding activity, but also from extracts of cells activated with phorbol esters and calcium ionophore, a combination of stimuli that triggered the simultaneous activation of NFAT and NF-kappaB. These results implicate NFAT in the regulation of endothelial genes by physiological means and shed light on the mechanisms that switch on the gene expression program induced by VEGF and those regulating TF gene expression.
CitationMolecular and Cellular Biology, 19(3): 2032-2043
PublisherAmerican Society for Microbiology
- Selective inhibition of vascular endothelial growth factor-mediated angiogenesis by cyclosporin A: roles of the nuclear factor of activated T cells and cyclooxygenase 2.
- Authors: Hernández GL, Volpert OV, Iñiguez MA, Lorenzo E, Martínez-Martínez S, Grau R, Fresno M, Redondo JM
- Issue date: 2001 Mar 5
- Vav-Rac1-mediated activation of the c-Jun N-terminal kinase/c-Jun/AP-1 pathway plays a major role in stimulation of the distal NFAT site in the interleukin-2 gene promoter.
- Authors: Kaminuma O, Deckert M, Elly C, Liu YC, Altman A
- Issue date: 2001 May
- Oxidized phospholipids stimulate tissue factor expression in human endothelial cells via activation of ERK/EGR-1 and Ca(++)/NFAT.
- Authors: Bochkov VN, Mechtcheriakova D, Lucerna M, Huber J, Malli R, Graier WF, Hofer E, Binder BR, Leitinger N
- Issue date: 2002 Jan 1
- Specificity, diversity, and convergence in VEGF and TNF-alpha signaling events leading to tissue factor up-regulation via EGR-1 in endothelial cells.
- Authors: Mechtcheriakova D, Schabbauer G, Lucerna M, Clauss M, De Martin R, Binder BR, Hofer E
- Issue date: 2001 Jan
- The regulation of hypoxic genes by calcium involves c-Jun/AP-1, which cooperates with hypoxia-inducible factor 1 in response to hypoxia.
- Authors: Salnikow K, Kluz T, Costa M, Piquemal D, Demidenko ZN, Xie K, Blagosklonny MV
- Issue date: 2002 Mar
Showing items related by title, author, creator and subject.
Vascular endothelial growth factor and hypoxia-inducible factor-1α gene polymorphisms and coronary collateral formation in patients with coronary chronic total occlusions.Amoah, Vincent; Wrigley, Benjamin; Holroyd, Eric; Smallwood, Andrew; Armesilla, Angel L; Nevill, Alan M.; Cotton, James (SAGE Publications, 2016)We evaluated the association between two single nucleotide polymorphisms of the vascular endothelial growth factor gene and one of the hypoxia-inducible factor-1α gene and the degree of coronary collateral formation in patients with a coronary chronic total occlusion.
Activating transcription factor ATF2 negatively regulates the expression of endothelial notch ligandsOlivares, Ivonne; Kalyanakrishnan, Krithika; Ahmed, Suhail; Murcott, Clare; Wilkinson, Robert N; Cotton, James; Breitwieser, Wolfgang; Morris, Mark R; Armesilla, Angel L (BMJ Publishing Group Ltd and British Cardiovascular Society, 2019-05-01)
Acute rise of circulating vascular endothelial growth factor-A in patients with coronary artery disease following cardiothoracic surgery.Cotton, James M.; Mathur, A.; Hong, Ying; Brown, Angie S.; Martin, John F.; Erusalimsky, Jorge D.AIMS: Vascular endothelial growth factor-A (VEGF-A) is an angiogenic and vasoprotective molecule whose expression is modulated by hypoxia and inflammatory mediators. Here we have tested the hypothesis that plasma levels of VEGF-A are influenced by pre-existing coronary artery disease and by changes in circulating interleukin-6 (IL-6). METHODS AND RESULTS: Plasma VEGF-A and IL-6 were measured prior to and at various time intervals following surgery in individuals with angiographically normal coronary arteries requiring cardiac valve replacement (N group) and in patients with coronary artery disease and stable angina undergoing coronary artery bypass grafting (CAD group). Baseline VEGF-A levels were not significantly different in CAD (22.3+/-2.6 pg x ml(-1)) compared to the N group (14.9+/-2.9 pg x ml(-1)). Following cardiac surgery there was a significant rise of VEGF-A in CAD (P<0.0005 vs baseline), but not in the N group, reaching a maximum (approximately 2 fold increase) after 24 h. Surgery caused a rapid increase of plasma IL-6 in both groups, but the rise was significantly larger in CAD patients (P<0.0005 vs N) where it preceded the increase in VEGF-A. Furthermore, in patients with CAD there was a significant correlation between the change in VEGF-A and the change in IL-6 (P<0.04). CONCLUSION: These findings demonstrate that in patients with coronary artery disease cardiothoracic surgery leads to an acute rise in VEGF-A. We suggest that this rise may result from an interaction between the pre-existing atheromatous process and a systemic increase of inflammatory mediators.