Skip to main content
SpringerLink
Log in

Expression of Vascular Endothelial Growth Factor and Hypoxia-Inducible Factor 1α in the Myocardium

  • Chapter
Signal Transduction and Cardiac Hypertrophy

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 7))

  • 123 Accesses

Summary

Expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF-1α), a transcription factor involved in the VEGF induction, was examined in the myocardium. In the 10-day-old chick embryonic hearts and ventricular myocytes, the mRNA species encoding VEGF and HIF-1α were abundantly expressed even at the basal conditions. The steady-state levels of the VEGF mRNA were regulated by various protein kinases. In the cultured neonatal rat ventricular myocytes, VEGF expression was upregulated by lipopolysaccharide. These data suggest that VEGF and HIF-1α expressed in cardiac myocytes may play significant roles in cardiovascular development. Furthermore, the cardiac myocyte-derived VEGF may also contribute to the pathogenesis of systemic inflammatory response syndrome, including myocardial interstitial edema.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Levy AP, Tamargo, R, Brem, H, Nathans, D. 1989. An endothelial growth factor from the mouse neuroblastoma cell line NB 41. Growth Factors 2:9–19.

    Article  PubMed  CAS  Google Scholar 

  2. Ferrara N, Houck K, Jakeman L, Leung DW. 1992. Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev 13:18–32.

    PubMed  CAS  Google Scholar 

  3. Senger DR, Van de Water L, Brown LF, Nagy JA, Yeo KT, Yeo TK, Berse B, Jackman RW, Dvorak AM, Dvorak HF. 1993. Vascular permeability factor (VPF,VEGF) in tumor biology. Cancer Metastasis Rev 12:303–324.

    Article  PubMed  CAS  Google Scholar 

  4. Connolly DT, Heuvelman DM, Nelson R, Olander JV, Eppley BL, Delfino JJ, Siegel NR, Leimgruber RM, Feder J. 1989. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest 84:1470–1478.

    Article  PubMed  CAS  Google Scholar 

  5. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. 1989. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309.

    Article  PubMed  CAS  Google Scholar 

  6. Keck PJ, Hauser SD, Krivi G, Sanzo K, Warren T, Feder J, Connolly DT. 1989. Vascular permeability factor, an endothelial cell migration related to PDGF. Science 246:1309–1312.

    Article  PubMed  CAS  Google Scholar 

  7. Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kleckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C, Declercq C, Pawling J, Moons L, Collen D, Risau W, Nagy A. 1996. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380:435–439.

    Article  PubMed  CAS  Google Scholar 

  8. Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O’Shea KS, Powell-Braxton L, Hillan KJ, Moore MW. 1996. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380:439–442.

    Article  PubMed  CAS  Google Scholar 

  9. Connolly DT, Olander JV, Heuvelman D, Nelson R, Monsell R, Siegel N, Haymore BL, Leimgruber R, Feder J. 1989. Human vascular permeability factor, isolation from U937 cells. J Biol Chem 264: 20017–20024.

    PubMed  CAS  Google Scholar 

  10. Connolly DT. 1991. Vascular permeability factor: a unique regulator of blood vessel formation. J Cell Biochem 47:219–223.

    Article  PubMed  CAS  Google Scholar 

  11. Ladoux A, Freiin C. 1993. Hypoxia id a strong inducer of vascular endothelial growth factor mRNA expression in the heart. Biochem Biophys Res Commun 195:1005–1010.

    Article  PubMed  CAS  Google Scholar 

  12. Ladoux A, Freiin C. 1994. Cobalt stimulates the expression of vascular endothelial growth factor mRNA in rat cardiac cells. Biochem Biophys Res Commun 204:794–798

    Article  PubMed  CAS  Google Scholar 

  13. Banai S, Shweiki D, Pinson A, Chandra M, Lazarovici G, Keshet E. 1994. Upregulation of vascular endothelial growth factor expression induced by myocardial ischaemia: implications for coronary angiogenesis. Cardiovasc Res 28:1176–1179.

    Article  PubMed  CAS  Google Scholar 

  14. Hashimoto E, Ogita T, Nakaoka T, Matsuoka R, Takao A, Kira Y. 1994. Rapid induction of vascular endothelial growth factor by ischemia in rat heart. Am J Physiol 267:H1948–H1954.

    PubMed  CAS  Google Scholar 

  15. Levy AP, Levy NS, Loscalzo J, Calderone A, Takahashi N, Yeo K-T, Koren G, Colucci WS, Goldberg MA. 1995. Regulation of vascular endothelial growth factor in cardiac myocytes. Circ Res 76:758–766.

    Article  PubMed  CAS  Google Scholar 

  16. Semenza GL. 1999. Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annu Rev Cell Dev Biol 15:551–578.

    Article  PubMed  CAS  Google Scholar 

  17. Wang GL, Jian B-H, Rue EA, Semenza GL. 1995. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA 92:5510–5514.

    Article  PubMed  CAS  Google Scholar 

  18. Gradin K, McGuire J, Wenger RH, Kvietikova I, Whitelaw ML, Toftgård R, Tora L, Gassman M, PoeUinger L. 1996. Functional interference between hypoxia and dioxin signal transduction path-ways: competition for recruitment of the Arnt transcription factor. Mol Cell Biol 16:5221–5231.

    PubMed  CAS  Google Scholar 

  19. Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL. 1996. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 16:4604–4613.

    PubMed  CAS  Google Scholar 

  20. Iyer NV, Kotch LE, Agani F, Leung SW, Laughner E, Wenger RH, Gassmann M, Gearhart JD, Lawler AM, Yu AY, Semenza GL. 1998. Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1α. Genes Dev 12:149–162.

    Article  PubMed  CAS  Google Scholar 

  21. Ryan HE, Lo J, Johnson RS. 1998. HIF-1α is required for solid tumor formation and embryonic vascularization. EMBO J 17:3005–3015.

    Article  PubMed  CAS  Google Scholar 

  22. Kotch LE, Iyer NV, Laughner E, Semenza GL. 1999. Defective vascularization of HIF-1α-null embryo is not associated with VEGF deficiency but with mesenchymal cell death. Dev Biol 209:254–267.

    Article  PubMed  CAS  Google Scholar 

  23. Maltepe E, Schmidt JV, Baunoch D, Bradfield CA, Simon MC. 1997. Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT. Nature 386:403–407.

    Article  PubMed  CAS  Google Scholar 

  24. Sugishita Y, Takahashi T, Shimizu T, Yao A, Kinugawa K, Sugishita K, Harada K, Matsui H, Nagai R. 2000. Expression of genes encoding vascular endothelial growth factor and its Flk-a receptor in the chick embryonic heart. J Mol Cell Cardiol 32:1039–1051.

    Article  PubMed  CAS  Google Scholar 

  25. Sugishita Y, Shimizu T, Yao A, Kinugawa K, Nojiri T, Harada K, Matsui H, Nagai R, Takahashi T. 2000. Lipopolysaccharide augments expression and secretion of vascular endothelial growth factor in rat ventricular myocytes. Biochem Biophys Res Commun 268:657–662.

    Article  PubMed  CAS  Google Scholar 

  26. Takahashi T, Sugishita Y, Nojiri T, Shimizu T, Yao A, Kinugawa K, Harada K, Nagai R. 2001. Cloning of hypoxia-inducible factor 1α cDNA from chick embryonic ventricular myocytes. Biochem Biophys Res Commun 281:1057–1062.

    Article  PubMed  CAS  Google Scholar 

  27. Flamme I, von Reutern M, Drexler HC, Syed-Ali S, Risau W. 1995. Overexpression of vascular endothelial growth factor in the avian embryo induces hypervascularization and increased vascular permeability without alterations of embryonic pattern formation. Dev Biol 171:399–414.

    Article  PubMed  CAS  Google Scholar 

  28. Tischer E, Mitchell R, Hartman T, Silva M, Gospodarowicz D, Fiddes JC, Abraham JA. The human gene for vascular endothelial growth factor. 1991. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem 266:11947–11954.

    PubMed  CAS  Google Scholar 

  29. Shima DT, Kuroki M, Deutsch U, Ng Y-S, Adamis AP, D’Amore PA. The mouse gene for vascular endothelial growth factor. 1996. Genomic structure, definition of the transcriptional unit, and characterization of transcriptional and post-transcriptional regulatory sequences. J Biol Chem 271:3877–3883.

    Article  PubMed  CAS  Google Scholar 

  30. Favier J, Kempf H, Corvol P, Gase J-M. 1999. Cloning and expression pattern of EPAS1 in the chicken embryo. Colocalization with tyrosine hydroxylase. FEBS Lett 462:19–24.

    Article  PubMed  CAS  Google Scholar 

  31. Tian H, Hammer RE, Matsumoto AM, Russel DW, McKnight SL. 1998. The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development. Genes Dev 12:3320–3324.

    Article  PubMed  CAS  Google Scholar 

  32. Gotloib L, Shostak A, Galdi P, Jaichenko J, Fudin R. 1992. Loss of microvascular negative charges accompanied by interstitial edema in septic rats’ heart. Circ Shock 36:45–56.

    PubMed  CAS  Google Scholar 

  33. Fukui M, Qiao Y, Guo F, Asano G. 1995. Cell damage and liberation of nitric oxide synthase in rat heart by endotoxin administration. J Nippon Med Sch 62:469–481.

    CAS  Google Scholar 

  34. Goddard CM, Allard MF, Hogg JC, Walley KR. 1996. Myocardial morphometric changes related to decreased contractility after endotoxin. Am J Physiol 270:H1446–H1452.

    PubMed  CAS  Google Scholar 

  35. Kinugawa K, Kohmoto O, Yao A, Serizawa T, Takahashi T. 1997. Cardiac inducible nitric oxide synthase negatively modulates myocardial function in cultured rat myocytes. Am J Physiol 272:H35–H47.

    PubMed  CAS  Google Scholar 

  36. Kinugawa K, Shimizu T, Yao, A, Kohmoto O, Serizawa T, Takahashi T. 1997. Transcriptional regulation of inducible nitric oxide synthase in cultured neonatal rat cardiac myocytes. Circ Res 81:911–921.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Toshiyuki Takahashi MD, Yasuyuki Sugishita, Tatsuya Shimizu, Atsushi Yao, Kazumasa Harada & Ryozo Nagai

Authors
  1. Toshiyuki Takahashi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasuyuki Sugishita
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tatsuya Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Atsushi Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kazumasa Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ryozo Nagai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Toshiyuki Takahashi MD .

Editor information

Editors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director), Larry V. Hryshko PhD (Associate Professor), Elissavet Kardami PhD (Professor) & Pawan K. Singal PhD, DSc (Professor) (Distinguished Professor and Director),  (Associate Professor),  (Professor) &  (Professor)

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Takahashi, T., Sugishita, Y., Shimizu, T., Yao, A., Harada, K., Nagai, R. (2003). Expression of Vascular Endothelial Growth Factor and Hypoxia-Inducible Factor 1α in the Myocardium. In: Dhalla, N.S., Hryshko, L.V., Kardami, E., Singal, P.K. (eds) Signal Transduction and Cardiac Hypertrophy. Progress in Experimental Cardiology, vol 7. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0347-7_32

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-0347-7_32

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5032-3

  • Online ISBN: 978-1-4615-0347-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation