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Assessment of Myocardial Angiogenesis and Vascularity in Small Animal Models

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Stem Cells for Myocardial Regeneration

Part of the book series: Methods in Molecular Biology ((MIMB,volume 660))

Abstract

Therapies that aim to prevent myocardial tissue from dying or to regenerate new myocardium all rely on the preservation or growth of a functional vasculature. The amount of blood that supplies the myocardium is dependent on the number and nature of the microvessels, as well as the ability of the arteries to supply blood and the veins to remove it. All of these factors can be assessed when success of an experimental therapy is being evaluated. Different kinds of information can be obtained from these different parameters, and it is important to understand what each one involves and how it can be misinterpreted. This chapter describes the various approaches to the assessment of vascularity in the heart with a focus on small animal models, dealing both with those approaches that are purely histological endpoint studies and those that are functional measurements in living animals.

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References

  1. Lu, Q. L., and Partridge, T. A. (1998) A new blocking method for application of murine monoclonal antibody to mouse tissue sections. J Histochem Cytochem 46, 977–84.

    Article  PubMed  CAS  Google Scholar 

  2. Takeshita, S., Zheng, L. P., Brogi, E., Kearney, M., Pu, L. Q., Bunting, S., Ferrara, N., Symes, J. F., and Isner, J. M. (1994) Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. J Clin Invest 93, 662–70.

    Article  PubMed  CAS  Google Scholar 

  3. Ushiki, T., and Abe, K. (1998) Identification of arterial and venous segments of blood vessels using alkaline phosphatase staining of ink/gelatin injected tissues. Arch Histol Cytol 61, 215–9.

    Article  PubMed  CAS  Google Scholar 

  4. Springer, M. L., Ozawa, C. R., Banfi, A., Kraft, P. E., Ip, T. K., Brazelton, T. R., and Blau, H. M. (2003) Localized arteriole formation directly adjacent to the site of VEGF-induced angiogenesis in muscle. Mol Ther 7, 441–9.

    Article  PubMed  CAS  Google Scholar 

  5. Tsurumi, Y., Takeshita, S., Chen, D., Kearney, M., Rossow, S. T., Passeri, J., Horowitz, J. R., Symes, J. F., and Isner, J. M. (1996) Direct intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor augments collateral development and tissue perfusion. Circulation 94, 3281–90.

    Article  PubMed  CAS  Google Scholar 

  6. Suri, C., McClain, J., Thurston, G., McDonald, D. M., Zhou, H., Oldmixon, E. H., Sato, T. N., and Yancopoulos, G. D. (1998) Increased vascularization in mice overexpressing angiopoietin-1. Science 282, 468–71.

    Article  PubMed  CAS  Google Scholar 

  7. Ozawa, C. R., Banfi, A., Glazer, N. L., Thurston, G., Springer, M. L., Kraft, P. E., McDonald, D. M., and Blau, H. M. (2004) Microenvironmental VEGF concentration, not total dose, determines a threshold between normal and aberrant angiogenesis. J Clin Invest 113, 516–27.

    PubMed  CAS  Google Scholar 

  8. Thurston, G., Baluk, P., Hirata, A., and McDonald, D. M. (1996) Permeability-related changes revealed at endothelial cell borders in inflamed venules by lectin binding. Am J Physiol 271, H2547–62.

    PubMed  CAS  Google Scholar 

  9. Zhao, Y. D., Courtman, D. W., Deng, Y., Kugathasan, L., Zhang, Q., and Stewart, D. J. (2005) Rescue of monocrotaline-induced pulmonary arterial hypertension using bone marrow-derived endothelial-like progenitor cells: efficacy of combined cell and eNOS gene therapy in established disease. Circ Res 96, 442–50.

    Article  PubMed  CAS  Google Scholar 

  10. Dutly, A. E., Kugathasan, L., Trogadis, J. E., Keshavjee, S. H., Stewart, D. J., and Courtman, D. W. (2006) Fluorescent microangiography (FMA): an improved tool to visualize the pulmonary microvasculature. Lab Invest 86, 409–16.

    Article  PubMed  Google Scholar 

  11. Jasper, M. S., McDermott, P., Gann, D. S., and Engeland, W. C. (1990) Measurement of blood flow to the adrenal capsule, cortex and medulla in dogs after hemorrhage by fluorescent microspheres. J Auton Nerv Syst 30, 159–67.

    Article  PubMed  CAS  Google Scholar 

  12. Kowallik, P., Schulz, R., Guth, B. D., Schade, A., Paffhausen, W., Gross, R., and Heusch, G. (1991) Measurement of regional myocardial blood flow with multiple colored microspheres. Circulation 83, 974–82.

    Article  PubMed  CAS  Google Scholar 

  13. Rissanen, T. T., Korpisalo, P., Markkanen, J. E., Liimatainen, T., Orden, M. R., Kholova, I., de Goede, A., Heikura, T., Grohn, O. H., and Ylä-Herttuala, S. (2005) Blood flow remodels growing vasculature during vascular endothelial growth factor gene therapy and determines between capillary arterialization and sprouting angiogenesis. Circulation 112, 3937–46.

    Article  PubMed  CAS  Google Scholar 

  14. Springer, M. L., Ip, T. K., and Blau, H. M. (2000) Angiogenesis monitored by perfusion with a space-filling microbead suspension. Mol Therapy 1, 82–7.

    Article  CAS  Google Scholar 

  15. Christman, K. L., Fang, Q., Yee, M. S., Johnson, K. R., Sievers, R. E., and Lee, R. J. (2005) Enhanced neovasculature formation in ischemic myocardium following delivery of pleiotrophin plasmid in a biopolymer. Biomaterials 26, 1139–44.

    Article  PubMed  CAS  Google Scholar 

  16. Leong-Poi, H., Kuliszewski, M. A., Lekas, M., Sibbald, M., Teichert-Kuliszewska, K., Klibanov, A. L., Stewart, D. J., and Lindner, J. R. (2007) Therapeutic arteriogenesis by ultrasound-mediated VEGF165 plasmid gene delivery to chronically ischemic skeletal muscle. Circ Res 101, 295–303.

    Article  PubMed  CAS  Google Scholar 

  17. Kaufmann, B. A., Lankford, M., Behm, C. Z., French, B. A., Klibanov, A. L., Xu, Y., and Lindner, J. R. (2007) High-resolution myocardial perfusion imaging in mice with high-frequency echocardiographic detection of a depot contrast agent. J Am Soc Echocardiogr 20, 136–43.

    Article  PubMed  Google Scholar 

  18. Lyshchik, A., Fleischer, A. C., Huamani, J., Hallahan, D. E., Brissova, M., and Gore, J. C. (2007) Molecular imaging of vascular endothelial growth factor receptor 2 expression using targeted contrast-enhanced high-frequency ultrasonography. J Ultrasound Med 26, 1575–86.

    PubMed  Google Scholar 

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Correspondence to Matthew L. Springer PhD .

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Springer, M.L. (2010). Assessment of Myocardial Angiogenesis and Vascularity in Small Animal Models. In: Lee, R. (eds) Stem Cells for Myocardial Regeneration. Methods in Molecular Biology, vol 660. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-705-1_10

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  • DOI: https://doi.org/10.1007/978-1-60761-705-1_10

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-704-4

  • Online ISBN: 978-1-60761-705-1

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