title: Plasma membrane calcium ATPase isoform 4 inhibits vascular endothelial growth factor-mediated angiogenesis through interaction with calcineurin.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: From the Molecular Pharmacology Group, School of Pharmacy (R.R.B., S.K., A.L.A.), Brain Tumor UK Neuro-oncology Research Centre (F.B.R.), and Oncology Group (W.W.), Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom; Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.A., D.L.-M., A.E., J.O., B.C.O., P.G.-d.A., S.M.-M., J.M.R.); Human Genetics Department, Institute for Rare Diseases Research, Carlos III Health Institute, Madrid, Spain (A.A.); Institute of Cardiovascular Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom (T.M.A.M., D.O., E.J.C., L.N.); Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt (T.M.A.M.); Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom (J.E.B.); Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain (P.G.-d.A.); and University of Luxembourg, Walferdange, Luxembourg (L.N.).
authors.forename: Rhiannon R
authors.initials: RR
authors.lastname: Baggott
authors.affiliation: From the Molecular Pharmacology Group, School of Pharmacy (R.R.B., S.K., A.L.A.), Brain Tumor UK Neuro-oncology Research Centre (F.B.R.), and Oncology Group (W.W.), Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom; Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.A., D.L.-M., A.E., J.O., B.C.O., P.G.-d.A., S.M.-M., J.M.R.); Human Genetics Department, Institute for Rare Diseases Research, Carlos III Health Institute, Madrid, Spain (A.A.); Institute of Cardiovascular Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom (T.M.A.M., D.O., E.J.C., L.N.); Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt (T.M.A.M.); Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom (J.E.B.); Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain (P.G.-d.A.); and University of Luxembourg, Walferdange, Luxembourg (L.N.).
authors.forename: Arantzazu
authors.initials: A
authors.lastname: Alfranca
authors.affiliation: From the Molecular Pharmacology Group, School of Pharmacy (R.R.B., S.K., A.L.A.), Brain Tumor UK Neuro-oncology Research Centre (F.B.R.), and Oncology Group (W.W.), Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom; Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.A., D.L.-M., A.E., J.O., B.C.O., P.G.-d.A., S.M.-M., J.M.R.); Human Genetics Department, Institute for Rare Diseases Research, Carlos III Health Institute, Madrid, Spain (A.A.); Institute of Cardiovascular Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom (T.M.A.M., D.O., E.J.C., L.N.); Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt (T.M.A.M.); Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom (J.E.B.); Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain (P.G.-d.A.); and University of Luxembourg, Walferdange, Luxembourg (L.N.).
authors.forename: Dolores
authors.initials: D
authors.lastname: López-Maderuelo
authors.affiliation: From the Molecular Pharmacology Group, School of Pharmacy (R.R.B., S.K., A.L.A.), Brain Tumor UK Neuro-oncology Research Centre (F.B.R.), and Oncology Group (W.W.), Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom; Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.A., D.L.-M., A.E., J.O., B.C.O., P.G.-d.A., S.M.-M., J.M.R.); Human Genetics Department, Institute for Rare Diseases Research, Carlos III Health Institute, Madrid, Spain (A.A.); Institute of Cardiovascular Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom (T.M.A.M., D.O., E.J.C., L.N.); Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt (T.M.A.M.); Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom (J.E.B.); Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain (P.G.-d.A.); and University of Luxembourg, Walferdange, Luxembourg (L.N.).
authors.forename: Tamer M A
authors.initials: TM
authors.lastname: Mohamed
authors.affiliation: From the Molecular Pharmacology Group, School of Pharmacy (R.R.B., S.K., A.L.A.), Brain Tumor UK Neuro-oncology Research Centre (F.B.R.), and Oncology Group (W.W.), Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom; Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.A., D.L.-M., A.E., J.O., B.C.O., P.G.-d.A., S.M.-M., J.M.R.); Human Genetics Department, Institute for Rare Diseases Research, Carlos III Health Institute, Madrid, Spain (A.A.); Institute of Cardiovascular Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom (T.M.A.M., D.O., E.J.C., L.N.); Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt (T.M.A.M.); Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom (J.E.B.); Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain (P.G.-d.A.); and University of Luxembourg, Walferdange, Luxembourg (L.N.).
authors.forename: Amelia
authors.initials: A
authors.lastname: Escolano
authors.affiliation: From the Molecular Pharmacology Group, School of Pharmacy (R.R.B., S.K., A.L.A.), Brain Tumor UK Neuro-oncology Research Centre (F.B.R.), and Oncology Group (W.W.), Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom; Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.A., D.L.-M., A.E., J.O., B.C.O., P.G.-d.A., S.M.-M., J.M.R.); Human Genetics Department, Institute for Rare Diseases Research, Carlos III Health Institute, Madrid, Spain (A.A.); Institute of Cardiovascular Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom (T.M.A.M., D.O., E.J.C., L.N.); Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt (T.M.A.M.); Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom (J.E.B.); Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain (P.G.-d.A.); and University of Luxembourg, Walferdange, Luxembourg (L.N.).
authors.forename: Jorge
authors.initials: J
authors.lastname: Oller
authors.affiliation: From the Molecular Pharmacology Group, School of Pharmacy (R.R.B., S.K., A.L.A.), Brain Tumor UK Neuro-oncology Research Centre (F.B.R.), and Oncology Group (W.W.), Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom; Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.A., D.L.-M., A.E., J.O., B.C.O., P.G.-d.A., S.M.-M., J.M.R.); Human Genetics Department, Institute for Rare Diseases Research, Carlos III Health Institute, Madrid, Spain (A.A.); Institute of Cardiovascular Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom (T.M.A.M., D.O., E.J.C., L.N.); Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt (T.M.A.M.); Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom (J.E.B.); Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain (P.G.-d.A.); and University of Luxembourg, Walferdange, Luxembourg (L.N.).
authors.forename: Beatriz C
authors.initials: BC
authors.lastname: Ornes
authors.affiliation: From the Molecular Pharmacology Group, School of Pharmacy (R.R.B., S.K., A.L.A.), Brain Tumor UK Neuro-oncology Research Centre (F.B.R.), and Oncology Group (W.W.), Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom; Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.A., D.L.-M., A.E., J.O., B.C.O., P.G.-d.A., S.M.-M., J.M.R.); Human Genetics Department, Institute for Rare Diseases Research, Carlos III Health Institute, Madrid, Spain (A.A.); Institute of Cardiovascular Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom (T.M.A.M., D.O., E.J.C., L.N.); Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt (T.M.A.M.); Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom (J.E.B.); Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain (P.G.-d.A.); and University of Luxembourg, Walferdange, Luxembourg (L.N.).
authors.forename: Sathishkumar
authors.initials: S
authors.lastname: Kurusamy
authors.affiliation: From the Molecular Pharmacology Group, School of Pharmacy (R.R.B., S.K., A.L.A.), Brain Tumor UK Neuro-oncology Research Centre (F.B.R.), and Oncology Group (W.W.), Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom; Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.A., D.L.-M., A.E., J.O., B.C.O., P.G.-d.A., S.M.-M., J.M.R.); Human Genetics Department, Institute for Rare Diseases Research, Carlos III Health Institute, Madrid, Spain (A.A.); Institute of Cardiovascular Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom (T.M.A.M., D.O., E.J.C., L.N.); Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt (T.M.A.M.); Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom (J.E.B.); Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain (P.G.-d.A.); and University of Luxembourg, Walferdange, Luxembourg (L.N.).
authors.forename: Farjana B
authors.initials: FB
authors.lastname: Rowther
authors.affiliation: From the Molecular Pharmacology Group, School of Pharmacy (R.R.B., S.K., A.L.A.), Brain Tumor UK Neuro-oncology Research Centre (F.B.R.), and Oncology Group (W.W.), Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom; Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.A., D.L.-M., A.E., J.O., B.C.O., P.G.-d.A., S.M.-M., J.M.R.); Human Genetics Department, Institute for Rare Diseases Research, Carlos III Health Institute, Madrid, Spain (A.A.); Institute of Cardiovascular Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom (T.M.A.M., D.O., E.J.C., L.N.); Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt (T.M.A.M.); Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom (J.E.B.); Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain (P.G.-d.A.); and University of Luxembourg, Walferdange, Luxembourg (L.N.).
authors.forename: James E
authors.initials: JE
authors.lastname: Brown
authors.affiliation: From the Molecular Pharmacology Group, School of Pharmacy (R.R.B., S.K., A.L.A.), Brain Tumor UK Neuro-oncology Research Centre (F.B.R.), and Oncology Group (W.W.), Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom; Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.A., D.L.-M., A.E., J.O., B.C.O., P.G.-d.A., S.M.-M., J.M.R.); Human Genetics Department, Institute for Rare Diseases Research, Carlos III Health Institute, Madrid, Spain (A.A.); Institute of Cardiovascular Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom (T.M.A.M., D.O., E.J.C., L.N.); Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt (T.M.A.M.); Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom (J.E.B.); Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain (P.G.-d.A.); and University of Luxembourg, Walferdange, Luxembourg (L.N.).
authors.forename: Delvac
authors.initials: D
authors.lastname: Oceandy
authors.affiliation: From the Molecular Pharmacology Group, School of Pharmacy (R.R.B., S.K., A.L.A.), Brain Tumor UK Neuro-oncology Research Centre (F.B.R.), and Oncology Group (W.W.), Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom; Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.A., D.L.-M., A.E., J.O., B.C.O., P.G.-d.A., S.M.-M., J.M.R.); Human Genetics Department, Institute for Rare Diseases Research, Carlos III Health Institute, Madrid, Spain (A.A.); Institute of Cardiovascular Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom (T.M.A.M., D.O., E.J.C., L.N.); Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt (T.M.A.M.); Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom (J.E.B.); Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain (P.G.-d.A.); and University of Luxembourg, Walferdange, Luxembourg (L.N.).
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Cartwright
authors.affiliation: From the Molecular Pharmacology Group, School of Pharmacy (R.R.B., S.K., A.L.A.), Brain Tumor UK Neuro-oncology Research Centre (F.B.R.), and Oncology Group (W.W.), Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom; Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.A., D.L.-M., A.E., J.O., B.C.O., P.G.-d.A., S.M.-M., J.M.R.); Human Genetics Department, Institute for Rare Diseases Research, Carlos III Health Institute, Madrid, Spain (A.A.); Institute of Cardiovascular Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom (T.M.A.M., D.O., E.J.C., L.N.); Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt (T.M.A.M.); Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom (J.E.B.); Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain (P.G.-d.A.); and University of Luxembourg, Walferdange, Luxembourg (L.N.).
authors.forename: Weiguang
authors.initials: W
authors.lastname: Wang
authors.affiliation: From the Molecular Pharmacology Group, School of Pharmacy (R.R.B., S.K., A.L.A.), Brain Tumor UK Neuro-oncology Research Centre (F.B.R.), and Oncology Group (W.W.), Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom; Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.A., D.L.-M., A.E., J.O., B.C.O., P.G.-d.A., S.M.-M., J.M.R.); Human Genetics Department, Institute for Rare Diseases Research, Carlos III Health Institute, Madrid, Spain (A.A.); Institute of Cardiovascular Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom (T.M.A.M., D.O., E.J.C., L.N.); Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt (T.M.A.M.); Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom (J.E.B.); Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain (P.G.-d.A.); and University of Luxembourg, Walferdange, Luxembourg (L.N.).
authors.forename: Pablo
authors.initials: P
authors.lastname: Gómez-del Arco
authors.affiliation: From the Molecular Pharmacology Group, School of Pharmacy (R.R.B., S.K., A.L.A.), Brain Tumor UK Neuro-oncology Research Centre (F.B.R.), and Oncology Group (W.W.), Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom; Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.A., D.L.-M., A.E., J.O., B.C.O., P.G.-d.A., S.M.-M., J.M.R.); Human Genetics Department, Institute for Rare Diseases Research, Carlos III Health Institute, Madrid, Spain (A.A.); Institute of Cardiovascular Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom (T.M.A.M., D.O., E.J.C., L.N.); Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt (T.M.A.M.); Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom (J.E.B.); Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain (P.G.-d.A.); and University of Luxembourg, Walferdange, Luxembourg (L.N.).
authors.forename: Sara
authors.initials: S
authors.lastname: Martínez-Martínez
authors.affiliation: From the Molecular Pharmacology Group, School of Pharmacy (R.R.B., S.K., A.L.A.), Brain Tumor UK Neuro-oncology Research Centre (F.B.R.), and Oncology Group (W.W.), Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom; Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.A., D.L.-M., A.E., J.O., B.C.O., P.G.-d.A., S.M.-M., J.M.R.); Human Genetics Department, Institute for Rare Diseases Research, Carlos III Health Institute, Madrid, Spain (A.A.); Institute of Cardiovascular Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom (T.M.A.M., D.O., E.J.C., L.N.); Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt (T.M.A.M.); Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom (J.E.B.); Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain (P.G.-d.A.); and University of Luxembourg, Walferdange, Luxembourg (L.N.).
authors.forename: Ludwig
authors.initials: L
authors.lastname: Neyses
authors.affiliation: From the Molecular Pharmacology Group, School of Pharmacy (R.R.B., S.K., A.L.A.), Brain Tumor UK Neuro-oncology Research Centre (F.B.R.), and Oncology Group (W.W.), Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom; Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.A., D.L.-M., A.E., J.O., B.C.O., P.G.-d.A., S.M.-M., J.M.R.); Human Genetics Department, Institute for Rare Diseases Research, Carlos III Health Institute, Madrid, Spain (A.A.); Institute of Cardiovascular Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom (T.M.A.M., D.O., E.J.C., L.N.); Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt (T.M.A.M.); Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom (J.E.B.); Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain (P.G.-d.A.); and University of Luxembourg, Walferdange, Luxembourg (L.N.). jmredondo@cnic.es A.Armesilla@wlv.ac.uk.
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Redondo
authors.affiliation: From the Molecular Pharmacology Group, School of Pharmacy (R.R.B., S.K., A.L.A.), Brain Tumor UK Neuro-oncology Research Centre (F.B.R.), and Oncology Group (W.W.), Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom; Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (A.A., D.L.-M., A.E., J.O., B.C.O., P.G.-d.A., S.M.-M., J.M.R.); Human Genetics Department, Institute for Rare Diseases Research, Carlos III Health Institute, Madrid, Spain (A.A.); Institute of Cardiovascular Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom (T.M.A.M., D.O., E.J.C., L.N.); Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt (T.M.A.M.); Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom (J.E.B.); Department of Molecular Biology, Universidad Autónoma de Madrid, Madrid, Spain (P.G.-d.A.); and University of Luxembourg, Walferdange, Luxembourg (L.N.). jmredondo@cnic.es A.Armesilla@wlv.ac.uk.
authors.forename: Angel Luis
authors.initials: AL
authors.lastname: Armesilla
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D057809:HEK293 Cells; D006614:Hindlimb; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007511:Ischemia / Q000201:enzymology / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D043925:Angiogenesis Inducing Agents; D019703:Calcineurin; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D051546:Cyclooxygenase 2; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D050778:NFATC Transcription Factors; D053499:Plasma Membrane Calcium-Transporting ATPases; D042461:Vascular Endothelial Growth Factor A; C511512:DSCR1 protein, mouse; C000589038:ATP2B4 protein, mouse; C108612:RCAN1 protein, human; C077623:Ptgs2 protein, mouse; C496540:PTGS2 protein, human; C507517:ATP2B4 protein, human
keywords: angiogenesis effect; calcineurin; calcium; nuclear factors of activated T cells; plasma membrane calcium–transporting ATPase