Advertisement

Journal of Membrane Biology

, Volume 227, Issue 3, pp 151–158 | Cite as

Hypoxic Modulation of Ca2+ Signaling in Human Venous and Arterial Endothelial Cells

  • P. K. Aley
  • C. C. Bauer
  • M. L. Dallas
  • J. P. Boyle
  • K. E. Porter
  • C. PeersEmail author
Short Communication

Abstract

Our understanding of vascular endothelial cell physiology is based on studies of endothelial cells cultured from various vascular beds of different species for varying periods of time. Systematic analysis of the properties of endothelial cells from different parts of the vasculature is lacking. Here, we compare Ca2+ homeostasis in primary cultures of endothelial cells from human internal mammary artery and saphenous vein and how this is modified by hypoxia, an inevitable consequence of bypass grafting (2.5% O2, 24 h). Basal [Ca2+] i and store depletion-mediated Ca2+ entry were significantly different between the two cell types, yet agonist (ATP)–mediated mobilization from endoplasmic reticulum stores was similar. Hypoxia potentiated agonist-evoked responses in arterial, but not venous, cells but augmented store depletion-mediated Ca2+ entry only in venous cells. Clearly, Ca2+ signaling and its remodeling by hypoxia are strikingly different in arterial vs. venous endothelial cells. Our data have important implications for the interpretation of data obtained from endothelial cells of varying sources.

Keywords

Ca2+ Hypoxia Endothelium Human tissue Vein Artery Ca2+ influx Ca2+ store 

References

  1. Abdallah Y, Gligorievski D, Kasseckert SA, Dieterich L, Schafer M, Kuhlmann CR, Noll T, Sauer H, Piper HM, Schafer C (2007) The role of poly(ADP-ribose) polymerase (PARP) in the autonomous proliferative response of endothelial cells to hypoxia. Cardiovasc Res 73:568–574PubMedCrossRefGoogle Scholar
  2. Arnould T, Michiels C, Alexandre I, Remacle J (1992) Effect of hypoxia upon intracellular calcium concentration of human endothelial cells. J Cell Physiol 152:215–221PubMedCrossRefGoogle Scholar
  3. Aromolaran AA, Blatter LA (2005) Modulation of intracellular Ca2+ release and capacitative Ca2+ entry by CaMKII inhibitors in bovine vascular endothelial cells. Am J Physiol 289:C1426–C1436CrossRefGoogle Scholar
  4. Bishara NB, Murphy TV, Hill MA (2002) Capacitative Ca2+ entry in vascular endothelial cells is mediated via pathways sensitive to 2 aminoethoxydiphenyl borate and xestospongin C. Br J Pharmacol 135:119–128PubMedCrossRefGoogle Scholar
  5. Bonnet S, Belus A, Hyvelin J-M, Roux E, Marthan R, Savineau J-P (2001) Effect of chronic hypoxia on agonist-induced tone and calcium signaling in rat pulmonary artery. Am J Physiol 281:L193–L201Google Scholar
  6. Budd JS, Allen KE, Bell PR (1991) Effects of two methods of endothelial cell seeding on cell retention during blood flow. Br J Surg 78:878–882PubMedCrossRefGoogle Scholar
  7. Cai H, Harrison DG (2000) Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 87:840–844PubMedGoogle Scholar
  8. Dedkova EN, Blatter LA (2002) Nitric oxide inhibits capacitative Ca2+ entry and enhances endoplasmic reticulum Ca2+ uptake in bovine vascular endothelial cells. J Physiol 539:77–91PubMedCrossRefGoogle Scholar
  9. Duchen MR (1992) Fluorescence-monitoring cell chemistry in vivo. In: Stamford JA (ed) Monitoring neuronal activity. Oxford University Press, Oxford, pp 231–260Google Scholar
  10. Fiorio PA, Munaron L (2001) Calcium influx, arachidonic acid, and control of endothelial cell proliferation. Cell Calcium 30:235–244CrossRefGoogle Scholar
  11. Galley HF, Webster NR (2004) Physiology of the endothelium. Br J Anaesth 93:105–113PubMedCrossRefGoogle Scholar
  12. Harrison DG, Cai H (2003) Endothelial control of vasomotion and nitric oxide production. Cardiol Clin 21:289–302PubMedCrossRefGoogle Scholar
  13. Hoebel BG, Kostner GM, Graier WF (1997) Activation of microsomal cytochrome P450 mono-oxygenase by Ca2+ store depletion and its contribution to Ca2+ entry in porcine aortic endothelial cells. Br J Pharmacol 121:1579–1588PubMedCrossRefGoogle Scholar
  14. Hu Q, Ziegelstein RC (2000) Hypoxia/reoxygenation stimulates intracellular calcium oscillations in human aortic endothelial cells. Circulation 102:2541–2547PubMedGoogle Scholar
  15. Kimura C, Oike M, Ito Y (2000) Hypoxia-induced alterations in Ca2+ mobilization in brain microvascular endothelial cells. Am J Physiol 279:H2310–H2318Google Scholar
  16. Klein CL, Kohler H, Bittinger F, Wagner M, Hermanns I, Grant K, Lewis JC, Kirkpatrick CJ (1994) Comparative studies on vascular endothelium in vitro. I. Cytokine effects on the expression of adhesion molecules by human umbilical vein, saphenous vein and femoral artery endothelial cells. Pathobiology 62:199–208PubMedCrossRefGoogle Scholar
  17. Li JM, Shah AM (2004) Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology. Am J Physiol 287:R1014–R1030Google Scholar
  18. Liu BF, Xu X, Fridman R, Muallem S, Kuo TH (1996) Consequences of functional expression of the plasma membrane Ca2+ pump isoform 1a. J Biol Chem 271:5536–5544PubMedCrossRefGoogle Scholar
  19. Lopez-Barneo J, Pardal R, Ortega-Saenz P (2001) Cellular mechanism of oxygen sensing. Annu Rev Physiol 63:259–287PubMedCrossRefGoogle Scholar
  20. Metzen E, Wolff M, Fandrey J, Jelkmann W (1995) Pericellular PO2 and O2 consumption in monolayer cell cultures. Respir Physiol 100:101–106PubMedCrossRefGoogle Scholar
  21. Michiels C, Arnould T, Remacle J (1993) Hypoxia-induced activation of endothelial cells as a possible cause of venous diseases—hypothesis. Angiology 44:639–646PubMedCrossRefGoogle Scholar
  22. Michiels C, Arnould T, ThibautVercruyssen R, Bouaziz N, Janssens D, Remacle J (1997) Perfused human saphenous veins for the study of the origin of varicose veins: role of the endothelium and of hypoxia. Int Angiol 16:134–141PubMedCrossRefGoogle Scholar
  23. Millar TM, Phan V, Tibbles LA (2007) ROS generation in endothelial hypoxia and reoxygenation stimulates MAP kinase signaling and kinase-dependent neutrophil recruitment. Free Radic Biol Med 42:1165–1177PubMedCrossRefGoogle Scholar
  24. Nilius B, Droogmans G (2001) Ion channels and their functional role in vascular endothelium. Physiol Rev 81:1415–1459PubMedGoogle Scholar
  25. Nilius B, Droogmans G, Wondergem R (2003) Transient receptor potential channels in endothelium: solving the calcium entry puzzle? Endothelium 10:5–15PubMedCrossRefGoogle Scholar
  26. Nwasokwa ON (1995) Coronary artery bypass graft disease. Ann Intern Med 123:528–545PubMedGoogle Scholar
  27. Paffett ML, Walker BR (2007) Vascular adaptations to hypoxia: molecular and cellular mechanisms regulating vascular tone. Essays Biochem 43:105–119PubMedCrossRefGoogle Scholar
  28. Pearlstein DP, Ali MH, Mungai PT, Hynes KL, Gewertz BL, Schumacker PT (2002) Role of mitochondrial oxidant generation in endothelial cell responses to hypoxia. Arterioscler Thromb Vasc Biol 22:566–573PubMedCrossRefGoogle Scholar
  29. Pearson PJ, Evora PR, Discigil B, Schaff HV (1998) Hypoxia increases vasodilator release from internal mammary artery and saphenous vein grafts. Ann Thorac Surg 65:1220–1225PubMedCrossRefGoogle Scholar
  30. Peers C (1997) Oxygen-sensitive ion channels. Trends Pharmacol Sci 18:405–408PubMedGoogle Scholar
  31. Peers C, Scragg JL, Boyle JP, Fearon IM, Taylor SC, Green KN, Webster NJ, Ramsden M, Pearson HA (2005) A central role for ROS in the functional remodelling of L-type Ca2+ channels by hypoxia. Philos Trans R Soc Lond B Biol Sci 360:2247–2254PubMedCrossRefGoogle Scholar
  32. Powell FL (2007) The influence of chronic hypoxia upon chemoreception. Respir Physiol Neurobiol 157:154–161PubMedCrossRefGoogle Scholar
  33. Sage SO, van Breemen C, Cannell MB (1991) Sodium–calcium exchange in cultured bovine pulmonary artery endothelial cells. J Physiol 440:569–580PubMedGoogle Scholar
  34. Schafer M, Ewald N, Schafer C, Stapler A, Piper HM, Noll T (2003) Signaling of hypoxia-induced autonomous proliferation of endothelial cells. FASEB J 17:449–451PubMedCrossRefGoogle Scholar
  35. Scoumanne A, Kalamati T, Moss J, Powell JT, Gosling M, Carey N (2002) Generation and characterisation of human saphenous vein endothelial cell lines. Atherosclerosis 160:59–67PubMedCrossRefGoogle Scholar
  36. Smith IF, Boyle JP, Plant LD, Pearson HA, Peers C (2003) Hypoxic remodeling of Ca2+ stores in type I cortical astrocytes. J Biol Chem 278:4875–4881PubMedCrossRefGoogle Scholar
  37. Tan PH, Chan C, Xue SA, Dong R, Ananthesayanan B, Manunta M, Kerouedan C, Cheshire NJ, Wolfe JH, Haskard DO, Taylor KM, George AJ (2004) Phenotypic and functional differences between human saphenous vein (HSVEC) and umbilical vein (HUVEC) endothelial cells. Atherosclerosis 173:171–183PubMedCrossRefGoogle Scholar
  38. Tiruppathi C, Minshall RD, Paria BC, Vogel SM, Malik AB (2002) Role of Ca2+ signaling in the regulation of endothelial permeability. Vascul Pharmacol 39:173–185PubMedCrossRefGoogle Scholar
  39. Tran QK, Ohashi K, Watanabe H (2000) Calcium signalling in endothelial cells. Cardiovasc Res 48:13–22PubMedCrossRefGoogle Scholar
  40. Unger RE, Krump-Konvalinkova V, Peters K, Kirkpatrick CJ (2002) In vitro expression of the endothelial phenotype: comparative study of primary isolated cells and cell lines, including the novel cell line HPMEC-ST1.6R. Microvasc Res 64:384–397PubMedCrossRefGoogle Scholar
  41. Webster NJ, Ramsden M, Boyle JP, Pearson HA, Peers C (2006) Amyloid peptides mediate hypoxic increase of L-type Ca2+ channels in central neurones. Neurobiol Aging 27:439–445PubMedCrossRefGoogle Scholar
  42. Yao X, Huang Y (2003) From nitric oxide to endothelial cytosolic Ca2+: a negative feedback control. Trends Pharmacol Sci 24:263–266PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • P. K. Aley
    • 1
    • 2
  • C. C. Bauer
    • 1
  • M. L. Dallas
    • 1
  • J. P. Boyle
    • 1
  • K. E. Porter
    • 1
  • C. Peers
    • 1
    Email author
  1. 1.Division of Cardiovascular and Neuronal Remodelling, Leeds Institute of Genetics, Health and Therapeutics, Faculty of Medicine and HealthUniversity of LeedsLeedsUK
  2. 2.Department of PharmacologyUniversity of OxfordOxfordUK

Personalised recommendations