Skip to main content
SpringerLink
Log in

Lung Ischemia: A Model for Endothelial Mechanotransduction

  • Review Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

Endothelial cells in vivo are constantly exposed to shear associated with blood flow and altered shear stress elicits cellular responses (mechanotransduction). This review describes the role of shear sensors and signal transducers in these events. The major focus is the response to removal of shear as occurs when blood flow is compromised (i.e., ischemia). Pulmonary ischemia studied with the isolated murine lung or flow adapted pulmonary microvascular endothelial cells in vitro results in endothelial generation of reactive oxygen species (ROS) and NO. The response requires caveolae and is initiated by endothelial cell depolarization via KATP channel closure followed by activation of NADPH oxidase (NOX2) and NO synthase (eNOS), signaling through MAP kinases, and endothelial cell proliferation. These physiological mediators can promote vasodilation and angiogenesis as compensation for decreased tissue perfusion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Szocs, K. (2004). Endothelial dysfunction and reactive oxygen species production in ischemia/reperfusion and nitrate tolerance. General Physiology and Biophysics, 23, 265–295.

    PubMed  CAS  Google Scholar 

  2. Kutala, V. K., Khan, M., Angelos, M. G., & Kuppusamy, P. (2007). Role of oxygen in postischemic myocardial injury. Antioxidants & Redox Signaling, 9, 1193–1206.

    Article  CAS  Google Scholar 

  3. McCord, J. M. (1985). Oxygen-derived free radicals in postischemic tissue injury. New England Journal of Medicine, 312, 159–163.

    PubMed  CAS  Google Scholar 

  4. Spisni, E., Bianco, M. C., Griffoni, C., Toni, M., D’ Angelo, R., Santi, S., et al. (2003). Mechanosensing role of caveolae and caveolar constituents in human endothelial cells. Journal of Cellular Physiology, 197, 198–204.

    Article  PubMed  CAS  Google Scholar 

  5. Barakat, A. I., & Davies, P. F. (1998). Mechanisms of shear stress transmission and transduction in endothelial cells. Chest, 114, 58S–63S.

    Article  PubMed  CAS  Google Scholar 

  6. Lansman, J. B. (1988). Endothelial mechanosensors. Going with the flow. Nature, 331, 481–482.

    Article  PubMed  CAS  Google Scholar 

  7. Davies, P. F., & Tripathi, S. C. (1993). Mechanical stress mechanisms and the cell. An endothelial paradigm. Circulation Research, 72, 239–245.

    PubMed  CAS  Google Scholar 

  8. Watson, P. A. (1991). Function follows form: Generation of intracellular signals by cell deformation. FASEB Journal, 5, 2013–2019.

    PubMed  CAS  Google Scholar 

  9. Davies, P. F., Barbee, K. A., Volin, M. V., Robotewskyj, A., Chen, J., Joseph, L., et al. (1997). Spatial relationships in early signaling events of flow-mediated endothelial mechanotransduction. Annual Review of Physiology, 59, 527–549.

    Article  PubMed  CAS  Google Scholar 

  10. Girard, P. R., & Nerem, R. M. (1993). Endothelial cell signaling and cytoskeletal changes in response to shear stress. Frontiers of Medical and Biological Engineering, 5, 31–36.

    PubMed  CAS  Google Scholar 

  11. Wei, Z., Costa, K., Al-Mehdi, A. B., Dodia, C., Muzykantov, V., & Fisher, A. B. (1999). Simulated ischemia in flow-adapted endothelial cells leads to generation of reactive oxygen species and cell signaling. Circulation Research, 85, 682–689.

    PubMed  CAS  Google Scholar 

  12. Chatterjee, S., Al-Mehdi, A. B., Levitan, I., Stevens, T., & Fisher, A. B. (2003). Shear stress increases expression of a KATP channel in rat and bovine pulmonary vascular endothelial cells. Am J Physiol Cell Physiol, 285, C959–C967.

    PubMed  CAS  Google Scholar 

  13. Kang-Decker, N., Cao, S., Chatterjee, S., Yao, J., Egan, L. J., Semela, D., et al. (2007). Nitric oxide promotes endothelial cell survival signaling through s-nitrosylation and activation of dynamin-2. Journal of Cell Science, 120, 492–501.

    Article  PubMed  CAS  Google Scholar 

  14. Fisher, A. B., Dodia, C., Tan, Z. T., Ayene, I., & Eckenhoff, R. G. (1991). Oxygen-dependent lipid peroxidation during lung ischemia. Journal of Clinical Investigation, 88, 674–679.

    Article  PubMed  CAS  Google Scholar 

  15. Ayene, I. S., Dodia, C., & Fisher, A. B. (1992). Role of oxygen in oxidation of lipid and protein during ischemia/reperfusion in isolated perfused rat lung. Archives of Biochemistry and Biophysics, 296, 183–189.

    Article  PubMed  CAS  Google Scholar 

  16. Al-Mehdi, A. B., Zhao, G., Dodia, C., Tozawa, K., Costa, K., Muzykantov, V., et al. (1998). Endothelial NADPH oxidase as the source of oxidants in lungs exposed to ischemia or high K+. Circulation Research, 83, 730–737.

    PubMed  CAS  Google Scholar 

  17. Olesen, S. P., Clapham, D. E., & Davies, P. F. (1988). Haemodynamic shear stress activates a K+ current in vascular endothelial cells. Nature, 331, 168–170.

    Article  PubMed  CAS  Google Scholar 

  18. Diamond, S. L., Sharefkin, J. B., Dieffenbach, C., Frasier-Scott, K., McIntire, L. V., & Eskin, S. G. (1990). Tissue plasminogen activator messenger rna levels increase in cultured human endothelial cells exposed to laminar shear stress. Journal of Cellular Physiology, 143, 364–371.

    Article  PubMed  CAS  Google Scholar 

  19. Davies, P. F. (1995). Flow-mediated endothelial mechanotransduction. Physiological Reviews, 75, 519–560.

    PubMed  CAS  Google Scholar 

  20. Resnick, N., Collins, T., Atkinson, W., Bonthron, D. T., Dewey, C. F., Jr, & Gimbron M. A., Jr. (1993). Platelet-derived growth factor b chain promoter contains a cis-acting fluid shear-stress-responsive element. [Erratum for Proc Natl Acad Sci U.S.A. 1993 May 15;90(10):4591–4595; pmid: 8506304]. Proceedings of the National Academy of Sciences of the United States of America, 90, 7908.

  21. Chien, S., Li, S., & Shyy, Y. J. (1998). Effects of mechanical forces on signal transduction and gene expression in endothelial cells. Hypertension, 31, 162–169.

    PubMed  CAS  Google Scholar 

  22. Davies, P. F. (2008). Endothelial transcriptome profiles in vivo in complex arterial flow fields. Annals of Biomedical Engineering, 36, 563–570.

    Article  PubMed  Google Scholar 

  23. Chien, S. (2006). Molecular basis of rheological modulation of endothelial functions: Importance of stress direction. Biorheology, 43, 95–116.

    PubMed  CAS  Google Scholar 

  24. Labrador, V., Chen, K. D., Li, Y. S., Muller, S., Stoltz, J. F., & Chien, S. (2003). Interactions of mechanotransduction pathways. Biorheology, 40, 47–52.

    PubMed  CAS  Google Scholar 

  25. Chen, K. D., Li, Y. S., Kim, M., Li, S., Yuan, S., Chien, S., et al. (1999). Mechanotransduction in response to shear stress. Roles of receptor tyrosine kinases, integrins, and shc. Journal of Biological Chemistry, 274, 18393–18400.

    Article  PubMed  CAS  Google Scholar 

  26. Liu, Y., Chen, B. P., Lu, M., Zhu, Y., Stemerman, M. B., Chien, S., et al. (2002). Shear stress activation of srebp1 in endothelial cells is mediated by integrins. Arteriosclerosis, Thrombosis, and Vascular Biology, 22, 76–81.

    Article  PubMed  Google Scholar 

  27. Wang, Y., Miao, H., Li, S., Chen, K. D., Li, Y. S., Yuan, S., et al. (2002). Interplay between integrins and flk-1 in shear stress-induced signaling. American Journal of Physiology—Cell Physiology, 283, C1540–C1547.

    PubMed  CAS  Google Scholar 

  28. Kuchan, M. J., Jo, H., & Frangos, J. A. (1994). Role of g proteins in shear stress-mediated nitric oxide production by endothelial cells. American Journal of Physiology, 267, C753–C758.

    PubMed  CAS  Google Scholar 

  29. Lieu, D. K., Pappone, P. A., & Barakat, A. I. (2004). Differential membrane potential and ion current responses to different types of shear stress in vascular endothelial cells. American Journal of Physiology—Cell Physiology, 286, C1367–C1375.

    Article  PubMed  CAS  Google Scholar 

  30. Traub, O., Ishida, T., Ishida, M., Tupper, J. C., & Berk, B. C. (1999). Shear stress-mediated extracellular signal-regulated kinase activation is regulated by sodium in endothelial cells. Potential role for a voltage-dependent sodium channel. Journal of Biological Chemistry, 274, 20144–20150.

    Article  PubMed  CAS  Google Scholar 

  31. Osawa, M., Masuda, M., Kusano, K., & Fujiwara, K. (2002). Evidence for a role of platelet endothelial cell adhesion molecule-1 in endothelial cell mechanosignal transduction: Is it a mechanoresponsive molecule? Journal of Cell Biology, 158, 773–785.

    Article  PubMed  CAS  Google Scholar 

  32. Weinbaum, S., Zhang, X., Han, Y., Vink, H., & Cowin, S. C. (2003). Mechanotransduction and flow across the endothelial glycocalyx. Proceedings of the National Academy of Sciences of the United States of America, 100, 7988–7995.

    Article  PubMed  CAS  Google Scholar 

  33. Tzima, E., Irani-Tehrani, M., Kiosses, W. B., Dejana, E., Schultz, D. A., Engelhardt, B., et al. (2005). A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature, 437, 426–431.

    Article  PubMed  CAS  Google Scholar 

  34. Cooke, J. P., Rossitch, E., Jr, Andon, N. A., Loscalzo, J., & Dzau, V. J. (1991). Flow activates an endothelial potassium channel to release an endogenous nitrovasodilator. Journal of Clinical Investigation, 88, 1663–1671.

    Article  PubMed  CAS  Google Scholar 

  35. Hoger, U., & Seyfarth, E. A. (2001). Structural correlates of mechanosensory transduction and adaptation in identified neurons of spider slit sensilla. Journal of Comparative Physiology. A, Sensory, Neural, and Behavioral Physiology, 187, 727–736.

    Article  PubMed  CAS  Google Scholar 

  36. Chatterjee, S., Levitan, I., Wei, Z., & Fisher, A. B. (2006). KATP channels are an important component of the shear-sensing mechanism in the pulmonary microvasculature. Microcirculation, 13, 633–644.

    Article  PubMed  CAS  Google Scholar 

  37. Milovanova, T., Chatterjee, S., Manevich, Y., Kotelnikova, I., Debolt, K., Madesh, M., et al. (2006). Lung endothelial cell proliferation with decreased shear stress is mediated by reactive oxygen species. American Journal of Physiology. Cell Physiology, 290, C66–C76.

    Article  PubMed  CAS  Google Scholar 

  38. Zhang, Q., Matsuzaki, I., Chatterjee, S., & Fisher, A. B. (2005). Activation of endothelial NADPH oxidase during normoxic lung ischemia is KATP channel dependent. Am J Physiol Lung Cell Mol Physiol, 289, L954–L961.

    Article  PubMed  CAS  Google Scholar 

  39. Milovanova, T., Chatterjee, S., Hawkins, B. J., Hong, N. K., Sorokina, E. M., DeBolt, K., Moore, J. S., Madesh, M., & Fisher, A. B. (2008). Caveolae are an essential component of the pathway for endothelial cell signaling associated with abrupt reduction of shear stress. Biochimica et Biophysica Acta, 1783, 1866–1875.

    Google Scholar 

  40. Sukharev, S., & Corey, D. P. (2004). Mechanosensitive channels: Multiplicity of families and gating paradigms. Science’s Stke [Electronic Resource]: Signal Transduction Knowledge Environment; re4.

  41. Maroto, R., Raso, A., Wood, T. G., Kurosky, A., Martinac, B., & Hamill, O. P. (2005). Trpc1 forms the stretch-activated cation channel in vertebrate cells [see comment]. Nature Cell Biology, 7, 179–185.

    Article  PubMed  CAS  Google Scholar 

  42. Geiger, B., Bershadsky, A., Pankov, R., & Yamada, K. M. (2001). Transmembrane crosstalk between the extracellular matrix—cytoskeleton crosstalk. Nature Reviews Molecular Cell Biology, 2, 793–805.

    Article  PubMed  CAS  Google Scholar 

  43. de Curtis, I., & Gatti, G. (1994). Identification of a large complex containing the integrin alpha 6 beta 1 laminin receptor in neural retinal cells. Journal of Cell Science, 107, 3165–3172.

    PubMed  Google Scholar 

  44. Jalali, S., del Pozo, M. A., Chen, K., Miao, H., Li, Y., Schwartz, M. A., et al. (2001). Integrin-mediated mechanotransduction requires its dynamic interaction with specific extracellular matrix (ecm) ligands. Proceedings of the National Academy of Sciences of the United States of America, 98, 1042–1046.

    Article  PubMed  CAS  Google Scholar 

  45. Li, S., Kim, M., Hu, Y. L., Jalali, S., Schlaepfer, D. D., Hunter, T., et al. (1997). Fluid shear stress activation of focal adhesion kinase. Linking to mitogen-activated protein kinases. Journal of Biological Chemistry, 272, 30455–30462.

    Article  PubMed  CAS  Google Scholar 

  46. Bhullar, I. S., Li, Y. S., Miao, H., Zandi, E., Kim, M., Shyy, J. Y., et al. (1998). Fluid shear stress activation of ikappab kinase is integrin-dependent. Journal of Biological Chemistry, 273, 30544–30549.

    Article  PubMed  CAS  Google Scholar 

  47. Radel, C., Carlile-Klusacek, M., & Rizzo, V. (2007). Participation of caveolae in beta1 integrin-mediated mechanotransduction. Biochemical and Biophysical Research Communications, 358, 626–631.

    Article  PubMed  CAS  Google Scholar 

  48. Kaufman, D. A., Albelda, S. M., Sun, J., & Davies, P. F. (2004). Role of lateral cell–cell border location and extracellular/transmembrane domains in pecam/cd31 mechanosensation. Biochemical and Biophysical Research Communications, 320, 1076–1081.

    Article  PubMed  CAS  Google Scholar 

  49. Manevich, Y., Al-Mehdi, A., Muzykantov, V., & Fisher, A. B. (2001). Oxidative burst and no generation as initial response to ischemia in flow-adapted endothelial cells. Am J Physiol Heart Circ Physiol, 280, H2126–H2135.

    PubMed  CAS  Google Scholar 

  50. Al-Mehdi, A. B., Shuman, H., & Fisher, A. B. (1997). Intracellular generation of reactive oxygen species during nonhypoxic lung ischemia. American Journal of Physiology, 272, L294–L300.

    PubMed  CAS  Google Scholar 

  51. Song, C., Al-Mehdi, A. B., & Fisher, A. B. (2001). An immediate endothelial cell signaling response to lung ischemia. American Journal of Physiology. Lung Cellular and Molecular Physiology, 281, L993–L1000, Corrigenda, 1282: Preceding L1167, 2002.

  52. Al-Mehdi, A. B., Shuman, H., Fisher, A. B., Shuman, H., & Fisher, A. B. (1997). Oxidant generation with K(+)-induced depolarization in the isolated perfused lung. Free Radical Biology and Medicine, 23, 47–56.

    Article  PubMed  CAS  Google Scholar 

  53. Zhang, Q., Chatterjee, S., Wei, Z., Liu, W. D., & Fisher, A. B. (2008). Rac and pi3 kinase mediate endothelial cell-reactive oxygen species generation during normoxic lung ischemia. Antioxidants & Redox Signaling, 10, 679–689.

    Article  CAS  Google Scholar 

  54. Tozawa, K., Al-Mehdi, A. B., Muzykantov, V., & Fisher, A. B. (1999). In situ imaging of intracellular calcium with ischemia in lung subpleural microvascular endothelial cells. Antioxidants Redox Signaling, 1, 145–154.

    Article  PubMed  CAS  Google Scholar 

  55. Matot, I., Manevich, Y., Al-Mehdi, A. B., Song, C., & Fisher, A. B. (2003). Fluorescence imaging of lipid peroxidation in isolated rat lungs during nonhypoxic lung ischemia. Free Radical Biology and Medicine, 34, 785–790.

    Article  PubMed  CAS  Google Scholar 

  56. Milovanova, T., Manevich, Y., Haddad, A., Chatterjee, S., Moore, J. S., & Fisher, A. B. (2004). Endothelial cell proliferation associated with abrupt reduction in shear stress is dependent on reactive oxygen species. Antioxidants Redox Signaling, 6, 245–258.

    Article  PubMed  CAS  Google Scholar 

  57. Matsuzaki, I., Chatterjee, S., Debolt, K., Manevich, Y., Zhang, Q., & Fisher, A. B. (2005). Membrane depolarization and NADPH oxidase activation in aortic endothelium during ischemia reflect altered mechanotransduction. American Journal of Physiology. Heart and Circulatory Physiology, 288, H336–H343.

    Article  PubMed  CAS  Google Scholar 

  58. Levitan, I., Helmke, B. P., & Davies, P. F. (2000). A chamber to permit invasive manipulation of adherent cells in laminar flow with minimal disturbance of the flow field. Annals of Biomedical Engineering, 28, 1184–1193.

    Article  PubMed  CAS  Google Scholar 

  59. Al-Mehdi, A. B., Zhao, G., & Fisher, A. B. (1998). ATP-independent membrane depolarization with ischemia in the oxygen-ventilated isolated rat lung. American Journal of Respiratory Cell and Molecular Biology, 18, 653–661.

    PubMed  CAS  Google Scholar 

  60. Al-Mehdi, A. B., Zhao, G., Tozawa, K., & Fisher, A. B. (2000). Depolarization-associated iron release with abrupt reduction in pulmonary endothelial shear stress in situ. Antioxidants Redox Signaling, 2, 335–345.

    Article  PubMed  CAS  Google Scholar 

  61. Wei, Z., Al-Mehdi, A. B., & Fisher, A. B. (2001). Signaling pathway for nitric oxide generation with simulated ischemia in flow-adapted endothelial cells. American Journal of Physiology. Heart and Circulatory Physiology, 281, H2226–H2232.

    PubMed  CAS  Google Scholar 

  62. Wei, Z., Manevich, Y., Al-Mehdi, A. B., Chatterjee, S., & Fisher, A. B. (2004). Ca2+ flux through voltage-gated channels with flow cessation in pulmonary microvascular endothelial cells. Microcirculation, 11, 517–526.

    Article  PubMed  CAS  Google Scholar 

  63. Haugland, R. P. (1996). Handbook of fluorescent probes and research chemicals (6th ed.). Eugene, OR.

  64. Al-Mehdi, A. B., Ischiropoulos, H., & Fisher, A. B. (1996). Endothelial cell oxidant generation during K(+)-induced membrane depolarization. Journal of Cellular Physiology, 166, 274–280.

    Article  PubMed  CAS  Google Scholar 

  65. Al-Mehdi, A. B., Song, C., Tozawa, K., & Fisher, A. B. (2000). Ca2+-and phosphatidylinositol 3-kinase-dependent nitric oxide generation in lung endothelial cells in situ with ischemia. Journal of Biological Chemistry, 275, 39807–39810.

    Article  PubMed  CAS  Google Scholar 

  66. Zhao, G., Al-Mehdi, A. B., & Fisher, A. B. (1997). Anoxia-reoxygenation versus ischemia in isolated rat lungs. American Journal of Physiology, 273, L1112–L1117.

    PubMed  CAS  Google Scholar 

  67. Jones, S. A., O’Donnell, V. B., Wood, J. D., Broughton, J. P., Hughes, E. J., & Jones, O. T. (1996). Expression of phagocyte NADPH oxidase components in human endothelial cells. American Journal of Physiology, 271, H1626–H1634.

    PubMed  CAS  Google Scholar 

  68. Babior, B. M. (2000). The NADPH oxidase of endothelial cells. IUBMB Life, 50, 267–269.

    Article  PubMed  CAS  Google Scholar 

  69. Zulueta, J. J., Sawhney, R., Yu, F. S., Cote, C. C., & Hassoun, P. M. (1997). Intracellular generation of reactive oxygen species in endothelial cells exposed to anoxia-reoxygenation. American Journal of Physiology, 272, L897–L902.

    PubMed  CAS  Google Scholar 

  70. Wu, S., Haynes, J., Jr, Taylor, J. T., Obiako, B. O., Stubbs, J. R., Li, M., et al. (2003). Cav3.1 (alpha1 g) t-type Ca2+ channels mediate vaso-occlusion of sickled erythrocytes in lung microcirculation. Circulation Research, 93, 346–353.

    Article  PubMed  CAS  Google Scholar 

  71. Rizzo, V., Sung, A., Oh, P., & Schnitzer, J. E. (1998). Rapid mechanotransduction in situ at the luminal cell surface of vascular endothelium and its caveolae. Journal of Biological Chemistry, 273, 26323–26329.

    Article  PubMed  CAS  Google Scholar 

  72. Rizzo, V., Morton, C., DePaola, N., Schnitzer, J. E., & Davies, P. F. (2003). Recruitment of endothelial caveolae into mechanotransduction pathways by flow conditioning in vitro. American Journal of Physiology. Heart and Circulatory Physiology, 285, H1720–H1729.

    PubMed  CAS  Google Scholar 

  73. Yu, J., Bergaya, S., Murata, T., Alp, I. F., Bauer, M. P., Lin, M. I., et al. (2006). Direct evidence for the role of caveolin-1 and caveolae in mechanotransduction and remodeling of blood vessels [see comment]. Journal of Clinical Investigation, 116, 1284–1291.

    Article  PubMed  CAS  Google Scholar 

  74. Sedding, D. G., Hermsen, J., Seay, U., Eickelberg, O., Kummer, W., Schwencke, C., et al. (2005). Caveolin-1 facilitates mechanosensitive protein kinase b (Akt) signaling in vitro and in vivo. Circulation Research, 96, 635–642.

    Article  PubMed  CAS  Google Scholar 

  75. Oh, P., & Schnitzer, J. E. (2001). Segregation of heterotrimeric g proteins in cell surface microdomains. G(q) binds caveolin to concentrate in caveolae, whereas g(i) and g(s) target lipid rafts by default. Molecular Biology of the Cell, 12, 685–698.

    PubMed  CAS  Google Scholar 

  76. Zhu, Y., Liao, H. L., Wang, N., Yuan, Y., Ma, K. S., Verna, L., et al. (2000). Lipoprotein promotes caveolin-1 and ras translocation to caveolae: Role of cholesterol in endothelial signaling. Arteriosclerosis, Thrombosis, and Vascular Biology, 20, 2465–2470.

    PubMed  CAS  Google Scholar 

  77. Gorodinsky, A., & Harris, D. A. (1995). Glycolipid-anchored proteins in neuroblastoma cells form detergent-resistant complexes without caveolin. Journal of Cell Biology, 129, 619–627.

    Article  PubMed  CAS  Google Scholar 

  78. Grill, H. P., Zweier, J. L., Kuppusamy, P., Weisfeldt, M. L., & Flaherty, J. T. (1992). Direct measurement of myocardial free radical generation in an in vivo model: Effects of postischemic reperfusion and treatment with human recombinant superoxide dismutase. Journal of the American College of Cardiology, 20, 1604–1611.

    Article  PubMed  CAS  Google Scholar 

  79. Udassin, R., Ariel, I., Haskel, Y., Kitrossky, N., & Chevion, M. (1991). Salicylate as an in vivo free radical trap: Studies on ischemic insult to the rat intestine. Free Radical Biology and Medicine, 10, 1–6.

    Article  PubMed  CAS  Google Scholar 

  80. Sohn, H. Y., Keller, M., Gloe, T., Morawietz, H., Rueckschloss, U., & Pohl, U. (2000). The small g-protein rac mediates depolarization-induced superoxide formation in human endothelial cells. Journal of Biological Chemistry, 275, 18745–18750.

    Article  PubMed  CAS  Google Scholar 

  81. Inoue, J., Gohda, J., Akiyama, T., & Semba, K. (2007). Nf-kappa b activation in development and progression of cancer. Cancer Science, 98, 268–274.

    Article  PubMed  CAS  Google Scholar 

  82. Sunters, A., Fernandez de Mattos, S., Stahl, M., Brosens, J. J., Zoumpoulidou, G., Saunders, C. A., et al. (2003). Foxo3a transcriptional regulation of bim controls apoptosis in paclitaxel-treated breast cancer cell lines. Journal of Biological Chemistry, 278, 49795–49805.

    Article  PubMed  CAS  Google Scholar 

  83. Meloche, S., & Pouyssegur, J. (2007). The erk1/2 mitogen-activated protein kinase pathway as a master regulator of the g1- to s-phase transition. Oncogene, 26, 3227–3239.

    Article  PubMed  CAS  Google Scholar 

  84. Wagner, E. M., Petrache, I., Schofield, B., & Mitzner, W. (2006). Pulmonary ischemia induces lung remodeling and angiogenesis. Journal of Applied Physiology, 100, 587–593.

    Article  PubMed  Google Scholar 

  85. Ushio-Fukai, M. (2007). VEGF signaling through NADPH oxidase-derived ROS. Antioxidants & Redox Signaling, 9, 731–739.

    Article  CAS  Google Scholar 

  86. Cameron, A. R., Nelson, J., & Forman, H. J. (1983). Depolarization and increased conductance precede superoxide release by concanavalin a-stimulated rat alveolar macrophages. Proceedings of the National Academy of Sciences of the United States of America, 80, 3726–3728.

    Article  PubMed  CAS  Google Scholar 

  87. Korchak, H. M., & Weissmann, G. (1978). Changes in membrane potential of human granulocytes antecede the metabolic responses to surface stimulation. Proceedings of the National Academy of Sciences of the United States of America, 75, 3818–3822.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Susan Turbitt for secretarial support and the many collaborators who have contributed to this research during the past 20 years. Original research has been supported by the NHLBI (HL79063, HL60290, and HL41939).

Author information

Authors and Affiliations

  1. Institute for Environmental Medicine, University of Pennsylvania Medical Center, 1 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA, 19104-6068, USA

    Shampa Chatterjee, Kenneth E. Chapman & Aron B. Fisher

Authors
  1. Shampa Chatterjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenneth E. Chapman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aron B. Fisher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aron B. Fisher.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chatterjee, S., Chapman, K.E. & Fisher, A.B. Lung Ischemia: A Model for Endothelial Mechanotransduction. Cell Biochem Biophys 52, 125–138 (2008). https://doi.org/10.1007/s12013-008-9030-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-008-9030-7

Keywords

Search

Navigation