Abstract
Successful therapeutic angiogenesis requires an understanding of how the myriad interactions of growth factors released during angiogenesis combine to form a mature vascular bed. This requires a model in which multiple physiological and cell biological parameters can be identified. The adenoviral-mediated mesenteric angiogenesis assay as described here is ideal for that purpose. The clear, thin, and relatively avascular mesenteric panel can be used to measure increased vessel perfusion by intravital microscopy. In addition, high-powered microvessel analysis is carried out by immunostaining of features essential for the study of angiogenesis or lymphangiogenesis (including endothelium, pericyte, smooth muscle cell area, and proliferation), allowing functional data to be obtained in conjunction with high-power microvessel ultrastructural analysis. Therefore, the mesenteric angiogenesis model offers a robust system to analyze the morphological changes associated with angiogenesis, induced by different agents.
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Wang WY et al (2004) An adenovirus-mediated gene-transfer model of angiogenesis in rat mesentery. Microcirculation 11(4):361–375
Rissanen TT et al (2003) VEGF-D is the strongest angiogenic and lymphangiogenic effector among VEGFs delivered into skeletal muscle via adenoviruses. Circ Res 92(10):1098–1106
Vajanto I et al (2002) Evaluation of angiogenesis and side effects in ischemic rabbit hindlimbs after intramuscular injection of adenoviral vectors encoding VEGF and LacZ. J Gene Med 4(4):371–380
Visconti RP, Richardson CD, Sato TN (2002) Orchestration of angiogenesis and arteriovenous contribution by angiopoietins and vascular endothelial growth factor (VEGF). Proc Natl Acad Sci U S A 99(12):8219–8224
Baluk P et al (2004) Regulated angiogenesis and vascular regression in mice overexpressing vascular endothelial growth factor in airways. Am J Pathol 165(4):1071–1085
Detmar M et al (1998) Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice. J Invest Dermatol 111(1):1–6
Sundberg C et al (2001) Glomeruloid microvascular proliferation follows adenoviral vascular permeability factor/vascular endothelial growth factor-164 gene delivery. Am J Pathol 158(3):1145–1160
Thurston G et al (2000) Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med 6(4):460–463
Cursiefen C et al (2004) VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J Clin Invest 113(7):1040–1050
Ziche M et al (1997) Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis. J Clin Invest 99(11):2625–2634
Glass CA, Harper SJ, Bates DO (2006) The anti-angiogenic VEGF isoform VEGF165b transiently increases hydraulic conductivity, probably through VEGF receptor 1 in vivo. J Physiol 572(Pt 1):243–257
Bates DO (1998) The chronic effect of vascular endothelial growth factor on individually perfused frog mesenteric microvessels. J Physiol 513(Pt 1):225–233
Dietrich HH (1989) Effect of locally applied epinephrine and norepinephrine on blood flow and diameter in capillaries of rat mesentery. Microvasc Res 38(2):125–135
Takano H et al (2004) Spreading dilatation in rat mesenteric arteries associated with calcium-independent endothelial cell hyperpolarization. J Physiol 556(Pt 3):887–903
Benest AV et al (2006) VEGF and angiopoietin-1 stimulate different angiogenic phenotypes that combine to enhance functional neovascularization in adult tissue. Microcirculation 13(6):423–437
Cristofaro B et al (2010) Neurotrophin-3 is a novel angiogenic factor capable of therapeutic neovascularization in a mouse model of limb ischemia. Arterioscler Thromb Vasc Biol 30(6):1143–1150
Benest AV et al (2008) VEGF-C induced angiogenesis preferentially occurs at a distance from lymphangiogenesis. Cardiovasc Res 78(2):315–323
Stone OA et al (2009) Critical role of tissue kallikrein in vessel formation and maturation: implications for therapeutic revascularization. Arterioscler Thromb Vasc Biol 29(5):657–664
Benest AV et al (2008) Arteriolar genesis and angiogenesis induced by endothelial nitric oxide synthase overexpression results in a mature vasculature. Arterioscler Thromb Vasc Biol 28(8):1462–1468
Schreihofer AM, Hair CD, Stepp DW (2005) Reduced plasma volume and mesenteric vascular reactivity in obese Zucker rats. Am J Physiol Regul Integr Comp Physiol 288(1):R253–R261
Sweat RS, Stapor PC, Murfee WL (2012) Relationships between lymphangiogenesis and angiogenesis during inflammation in rat mesentery microvascular networks. Lymphat Res Biol 10(4):198–207
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Benest, A.V., Bates, D.O. (2016). Measurement of Angiogenesis, Arteriolargenesis, and Lymphangiogenesis Phenotypes by Use of Two-Dimensional Mesenteric Angiogenesis Assay. In: Martin, S., Hewett, P. (eds) Angiogenesis Protocols. Methods in Molecular Biology, vol 1430. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3628-1_24
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DOI: https://doi.org/10.1007/978-1-4939-3628-1_24
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Publisher Name: Humana Press, New York, NY
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