Skip to main content

Advertisement

Log in

Effect of Angiogenesis Induced by Consecutive Intramuscular Injections of Vascular Endothelial Growth Factor in a Hindlimb Ischemic Mouse Model

  • Original Article
  • Published:
Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Angiogenesis plays a major role in various physiological and pathological situations. Thus, an angiogenic therapy with vascular endothelial growth factor (VEGF) has been commonly recommended as a representative therapeutic solution to recover the insufficient blood supply of collateral vessels in an ischemic lesion. In this study, the injection method and injection time point of VEGF proteins were focused to discover how to enhance the angiogenic effect with VEGF.

Methods

Mouse models (n = 15) were divided into control, VEGF treatment by intra-venous injection (VEGF-IV) and VEGF treatment by intra-muscular injection (VEGF-IM). Right proximal femoral arteries of mice were firmly sutured to obstruct arterial blood-flow. In the VEGF-IV treatment group, VEGF proteins were injected into the tail vein and, in the VEGF-IM treatment group, VEGF proteins were directly injected into the ischemic site of the right thigh after postoperative day 5, 10, 15, 20 and 25 follow-ups. Blood-flow images were acquired by 99mTc Gamma Image Acquisition System to compare the ischemic-to-non-ischemic bloodstream ratio at postoperative days 5, 15, and 30.

Results

VEGF-IM treatment significantly induced higher an angiogenic effect rather than both the control group (P = 0.008) and VEGF-IV treatment group (P = 0.039) at the 30th day.

Conclusion

During all experiments, angiogenesis of VEGF-IM treatment represented the most evident effect compared with control and VEGF-IV group in a mouse model of hindlimb ischemia.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Al SH. Therapeutic angiogenesis in cardiovascular disease. J Cardiothorac Surg. 2007;2:49.

    Article  Google Scholar 

  2. Ahn SH, Min SI, Kin SY, Min SK, Yang HK, Kim SJ, et al. Effect of nanoparticle with VEGF in mouse ischemic hindlimb model. J Korean Surg Soc. 2010;79:294–9.

    Article  Google Scholar 

  3. Wahlberg E. Angiogenesis and arteriogenesis in limb ischemia. J Vasc Surg. 2003;38:198–203.

    Article  PubMed  Google Scholar 

  4. Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004;56:549–80.

    Article  CAS  PubMed  Google Scholar 

  5. Biscetti F, Straface G, Arena V, Stigliano E, Pecorini G, Rizzo P. Pioglitazone enhances collateral blood flow in ischemic hindlimb of diabetic mice through an Akt-dependent VEGF-mediated mechanism, regardless of PPARγ stimulation. Cardiovasc Diabetol. 2009;8:49.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Zhu WH, Maclntyre A, Nicosia RF. Regulation of angiogenesis by vascular endothelial growth factor and angiopoietin-1 in the rat aorta model. Am J Pathol. 2002;161(3):823–30.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Yamada K, Ushio Y, Hayakawa T, Kalo A, Yamada N, Mogami H. Quantitative autoradiographic measurements of blood–brain barrier permeability in the rat glioma model. J Neurosurg. 1982;57:394–8.

    Article  CAS  PubMed  Google Scholar 

  8. Falcon BL, Barr S, Gokhale PC, Chou J, Fogarty J, Depeille P, et al. Reduced VEGF production, angiogenesis, and vascular regrowth contribute to the antitumor properties of dual mTORC1/mTORC2 inhibitors. Cancer Res. 2011;71(5):1573–83.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Baelde HJ, Eikmans M, Lappin DW, Doran PP, Hohenadel D, Brinkkoetter PT, et al. Reduction of VEGF-A and CTGF expression in diabetic nephropathy is associated with podocyte loss. Kidney Int. 2007;71(7):637–45.

    Article  CAS  PubMed  Google Scholar 

  10. Jośko J, Gwóźdź B, Jedrzejowska-Szypułka H, Hendryk S. Vascular endothelial growth factor (VEGF) and its effect on angiogenesis. Med Sci Monit. 2000;6(5):1047–52.

    PubMed  Google Scholar 

  11. Lee YS. Radiopharmaceuticals for molecular imaging. Open Nucl Med J. 2010;2:178–85.

    Article  Google Scholar 

  12. Min JJ. Monitoring gene therapy by radionuclide approaches. Nucl Med Mol Imaging. 2006;40(2):96–105.

    Google Scholar 

Download references

Acknowledgments

This study was supported by the Radiation Technology R&D program through the National Research Foundation of Korea Grant funded by the Ministry of Education, Science and Technology (2012-M2A2A7035779, 2011-0028581, 2009-0078422) and Research Funds of Chonbuk National University in 2012.

Conflicts of Interest

Tai Kyoung Lee, Chang-Moon Lee, Hyosook Hwang, Kyung Sook Na, JeongIl Kwon, Hwan-Seok Jeong, Philsun Oh, Hee Kwon Kim, Seok Tae Lim, Myung-Hee Sohn, and Hwan-Jeong Jeong declare that they have no conflict of interest.

Ethical Statement

This study was approved by the animal ethics committee in our hospital and was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hwan-Jeong Jeong.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, T.K., Hwang, H., Na, K.S. et al. Effect of Angiogenesis Induced by Consecutive Intramuscular Injections of Vascular Endothelial Growth Factor in a Hindlimb Ischemic Mouse Model. Nucl Med Mol Imaging 48, 225–229 (2014). https://doi.org/10.1007/s13139-014-0273-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13139-014-0273-5

Keywords

Navigation