Mechanism of Controlling Blood Vessel Growth and Development and Identification of Therapeutics Against Pathological Angiogenesis

Blood vessel formation during vertebrate development relies on a process called angiogenesis and is essential for organ growth and tissue viability. In addition, angiogenesis leads to pathological blood vessel growth in diseases with tissue ischaemia, such as neovascular eye disease and cancer. Neuropilin 1 (NRP1) is a transmembrane protein that serves as a receptor for the VEGF165 isoform of the vascular endothelial growth factor (VEGF) to enhance cell migration during angiogenesis via VEGF receptor 2 (VEGFR2), and it is also essential for VEGF-induced vascular permeability and arteriogenesis. In addition, NRP1 activation affects angiogenesis independently of VEGF signalling by activating the intracellular kinase ABL1. NRP1 also acts as a receptor for the class 3 semaphorin (SEMA3A) to regulate vessel maturation during tumour angiogenesis and vascular permeability in eye disease. In the present paper, we review current knowledge of NRP1 regulation during angiogenesis and vascular pathology.

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Blood Vessel Growth: Mathematical Analysis and Computer Simulation, Fractality, and Optimality

Vascular Morphogenesis: In Vivo, In Vitro, In Mente ◽

10.1007/978-1-4612-4156-0_14 ◽

1996 ◽

pp. 189-203 ◽

Cited By ~ 1

Author(s):

Haymo Kurz ◽

Konrad Sandau ◽

Jörg Wilting ◽

Bodo Christ

Keyword(s):

Computer Simulation ◽

Blood Vessel ◽

Mathematical Analysis ◽

Vessel Growth

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The influence of high glucose concentration on the ability of mesenchymal stromal cells to stimulate blood vessel growth

Diabetes Mellitus ◽

10.14341/2072-0351-5631 ◽

2011 ◽

Vol 14 (2) ◽

pp. 32-35 ◽

Cited By ~ 2

Author(s):

Zhanna Alekseevna Akopyan ◽

Georgy Vladimirovich Sharonov ◽

Tatiana Nikolaevna Kochegura ◽

Natalya Fedorovna Il'yashenko ◽

Igor Eduardovich Belyanko ◽

...

Keyword(s):

Adipose Tissue ◽

Blood Vessel ◽

High Glucose ◽

Glucose Concentration ◽

Functional Activity ◽

Human Adipose Tissue ◽

Diabetic Patients ◽

High Glucose Concentration ◽

Vessel Growth ◽

Negative Effect

Adipose issue is a source of mesenchymal stem cells (MSC) that can be used to stimulate blood vessel growth in ischemic tissues. Various metabolicdisorders including hypeglycemia may have negative effect on therapeutic properties of these cells. Aim. To study the influence of high glucose concentration on functional activity in human adipose tissue. Materials and methods. Flow cytometry and real time PCR were used to study functional activity of cultured MSC from human adipose issue at highglucose concentration. Results. Prolonged (10-12 days) incubation at a high glucose concentration (25 mM) suppressed the ability of MSC to stimulate angiogenesis. Also,glucose modified expression of genes activating and inhibiting angiogenesis but had no effect on MSC proliferation and apoptosis. Conclusion. High glucose concentration suppresses angiogenic activity of MSC in adipose tissue; it may account for incomplete restoration of bloodflow in diabetic patients.

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Sustained VEGF delivery via PLGA nanoparticles promotes vascular growth

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00199.2009 ◽

2010 ◽

Vol 298 (6) ◽

pp. H1959-H1965 ◽

Cited By ~ 92

Author(s):

Justin S. Golub ◽

Young-tae Kim ◽

Craig L. Duvall ◽

Ravi V. Bellamkonda ◽

Divya Gupta ◽

...

Keyword(s):

Tissue Engineering ◽

Blood Vessel ◽

Femoral Artery ◽

Release Kinetics ◽

Aortic Ring ◽

Plga Nanoparticles ◽

Cardiovascular Medicine ◽

Vessel Growth ◽

Vessel Volume

Technologies to increase tissue vascularity are critically important to the fields of tissue engineering and cardiovascular medicine. Currently, limited technologies exist to encourage angiogenesis and arteriogenesis in a controlled manner. In the present study, we describe an injectable controlled release system consisting of VEGF encapsulated in poly(lactic- co-glycolic acid) (PLGA) nanoparticles (NPs). The majority of VEGF was released gradually over 2–4 days from the NPs as determined by an ELISA release kinetics experiment. An in vitro aortic ring bioassay was used to verify the bioactivity of VEGF-NPs compared with empty NPs and no treatment. A mouse femoral artery ischemia model was then used to measure revascularization in VEGF-NP-treated limbs compared with limbs treated with naked VEGF and saline. 129/Sv mice were anesthetized with isoflurane, and a region of the common femoral artery and vein was ligated and excised. Mice were then injected with VEGF-NPs, naked VEGF, or saline. After 4 days, three-dimensional microcomputed tomography angiography was used to quantify vessel growth and morphology. Mice that received VEGF-NP treatment showed a significant increase in total vessel volume and vessel connectivity compared with 5 μg VEGF, 2.5 μg VEGF, and saline treatment (all P < 0.001). When the yield of the fabrication process was taken into account, VEGF-NPs were over an order of magnitude more potent than naked VEGF in increasing blood vessel volume. Differences between the VEGF-NP group and all other groups were even greater when only small-sized vessels under 300 μm diameter were analyzed. In conclusion, sustained VEGF delivery via PLGA NPs shows promise for encouraging blood vessel growth in tissue engineering and cardiovascular medicine applications.

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