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Erschienen in: Nuclear Medicine and Molecular Imaging 3/2014

01.09.2014 | Original Article

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

verfasst von: Tai Kyoung Lee, Hyosook Hwang, Kyung Sook Na, JeongIl Kwon, Hwan-Seok Jeong, Philsun Oh, Hee Kwon Kim, Seok Tae Lim, Myung-Hee Sohn, Hwan-Jeong Jeong, Chang-Moon Lee

Erschienen in: Nuclear Medicine and Molecular Imaging | Ausgabe 3/2014

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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.
Literatur
1.
Zurück zum Zitat Al SH. Therapeutic angiogenesis in cardiovascular disease. J Cardiothorac Surg. 2007;2:49.CrossRef Al SH. Therapeutic angiogenesis in cardiovascular disease. J Cardiothorac Surg. 2007;2:49.CrossRef
2.
Zurück zum Zitat 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.CrossRef 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.CrossRef
3.
Zurück zum Zitat Wahlberg E. Angiogenesis and arteriogenesis in limb ischemia. J Vasc Surg. 2003;38:198–203.PubMedCrossRef Wahlberg E. Angiogenesis and arteriogenesis in limb ischemia. J Vasc Surg. 2003;38:198–203.PubMedCrossRef
4.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
5.
Zurück zum Zitat 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
6.
Zurück zum Zitat 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
7.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
8.
Zurück zum Zitat 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
9.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
10.
Zurück zum Zitat 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 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
11.
Zurück zum Zitat Lee YS. Radiopharmaceuticals for molecular imaging. Open Nucl Med J. 2010;2:178–85.CrossRef Lee YS. Radiopharmaceuticals for molecular imaging. Open Nucl Med J. 2010;2:178–85.CrossRef
12.
Zurück zum Zitat Min JJ. Monitoring gene therapy by radionuclide approaches. Nucl Med Mol Imaging. 2006;40(2):96–105. Min JJ. Monitoring gene therapy by radionuclide approaches. Nucl Med Mol Imaging. 2006;40(2):96–105.
Metadaten
Titel
Effect of Angiogenesis Induced by Consecutive Intramuscular Injections of Vascular Endothelial Growth Factor in a Hindlimb Ischemic Mouse Model
verfasst von
Tai Kyoung Lee
Hyosook Hwang
Kyung Sook Na
JeongIl Kwon
Hwan-Seok Jeong
Philsun Oh
Hee Kwon Kim
Seok Tae Lim
Myung-Hee Sohn
Hwan-Jeong Jeong
Chang-Moon Lee
Publikationsdatum
01.09.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Nuclear Medicine and Molecular Imaging / Ausgabe 3/2014
Print ISSN: 1869-3474
Elektronische ISSN: 1869-3482
DOI
https://doi.org/10.1007/s13139-014-0273-5

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