Takahashi H, Shibuya MThe vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions. Clin Sci (Lond) 109: 227-241

Institute of Medical Science, The University of Tokyo, Tōkyō, Japan
Clinical Science (Impact Factor: 5.6). 10/2005; 109(3):227-41. DOI: 10.1042/CS20040370
Source: PubMed


The VEGF (vascular endothelial growth factor) family and its receptors are essential regulators of angiogenesis and vascular permeability. Currently, the VEGF family consists of VEGF-A, PlGF (placenta growth factor), VEGF-B, VEGF-C, VEGF-D, VEGF-E and snake venom VEGF. VEGF-A has at least nine subtypes due to the alternative splicing of a single gene. Although the VEGF165 isoform plays a central role in vascular development, recent studies have demonstrated that each VEGF isoform plays distinct roles in vascular patterning and arterial development. VEGF-A binds to and activates two tyrosine kinase receptors, VEGFR (VEGF receptor)-1 and VEGFR-2. VEGFR-2 mediates most of the endothelial growth and survival signals, but VEGFR-1-mediated signalling plays important roles in pathological conditions such as cancer, ischaemia and inflammation. In solid tumours, VEGF-A and its receptor are involved in carcinogenesis, invasion and distant metastasis as well as tumour angiogenesis. VEGF-A also has a neuroprotective effect on hypoxic motor neurons, and is a modifier of ALS (amyotrophic lateral sclerosis). Recent progress in the molecular and biological understanding of the VEGF/VEGFR system provides us with novel and promising therapeutic strategies and target proteins for overcoming a variety of diseases.

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    • "The rate of VEGF secretion is controlled through an auto-inhibitory regulatory mechanism where the VEGF concentration of a cell's microenvironment down-regulates the secretion of VEGF. This control loop enables a community of cells to maintain a stable background concentration of VEGF [23]. Disruption of the loop is implicated in multiple disease states. "

    CIBCB 2015; 08/2015
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    • "VEGFR-1/VEGF-A activation is involved in the induction of MMPs [14] [26]. VEGFR-2/VEGF-A activation is involved in angiogenesis [6] [7] [8] [9]. (Table 1 and Fig. 1 "
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    ABSTRACT: The pathophysiology of the chronicity and non-healing status of wounds remains unknown. This paper presents the following hypothesis: abnormal patterns of vascular endothelial growth factor receptors (VEGFRs) are the culprits of wound chronicity and non-healing. More specifically, for patients with poor circulation, the decreased VEGFR-2 level is the cause of poor wound healing; for patients with non-compromised circulation, for example, patients with concurrent chronic wounds and active autoimmune diseases, the increased VEGFR-1 level is related to the non-healing status of wounds. The hypothesis is supported by the following facts. VEGFR-1 is the main contributor for inflammation and VEGFR-2 facilitates angiogenesis; soluble VEGFR-1 (sVEGFR-1) inactivates both VEGFR-1 and VEGFR-2. Patients with auto-immune disease have abnormally increased VEGFR-1 and decreased sVEGFR. Wounds in patients with active autoimmune diseases have poor response to electric stimulation which facilitates chronic wound healing in patients without active autoimmune diseases via increasing vascular endothelial growth factor (VEGF) secretion. Patients with chronic wounds (including diabetic foot ulcers and venous leg ulcers) but no active autoimmune diseases have decreased VEGFR-2 levels. We thus believe that abnormal patterns of VEGFRs are the culprits of wound chronicity and non-healing. For wounds with compromised circulation, VEGFR-2 decrease contributes to its chronicity; whereas for wounds with non-compromised circulation, VEGFR-1 increase is the leading cause of the non-healing status of chronic wounds. Treatments and research in wound care should be tailored to target these changes based on circulation status of wounds. Complete elucidation of changes of VEGFRs in chronic and non-healing wounds will enhance our understandings in tissue healing and thus better our selection of appropriate treatments for chronic and non-healing wounds. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Medical Hypotheses 06/2015; DOI:10.1016/j.mehy.2015.06.017 · 1.07 Impact Factor
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    • "Again, the pathogenic role of VEGF in IPF is complex and also crucial through angiogenesis and extracellular matrix production by fibroblasts [24]; its inhibition reduces pulmonary fibrosis in mice [25]. On the other hand, soluble VEGF receptors 1 and 2 (sVEGFR-1 and -2) are important regulators of blood vessel growth and play an important role in maintaining the microvasculature [26]. Altogether, effects of Fig. 1. "
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    ABSTRACT: Background: Idiopathic pulmonary fibrosis (IPF) is associated with a marked pulmonary vascular remodeling. The aim of this study was to investigate a potential imbalance between angiogenic and angiostatic factors in this disease. Methods and results: Sixty-four subjects with IPF and 10 healthy control subjects (60-70 years old) were prospectively included in this multicenter study. Plasma levels of vascular endothelial growth factor A (VEGF-A), thrombospondin-1 (TSP-1) and stem cell factor (SCF) were determined by Elisa. Comparisons between IPF and controls were made using the Mann-Whitney U test. We also analyzed these soluble mediators in relation with IPF severity (DLCO<40% or>40%) predicted or total lung capacity (TLC) and forced vital capacity (FVC) (both<55% or>55% predicted) using the same test. VEGF-A plasma levels were increased in IPF vs. controls (P=0.0008) as well as those of TSP-1 (P=0.008), irrespective of the severity of the disease as reflected by DLCO, TLC or FVC values. In contrast, SCF levels were similar in IPF and controls. Conclusions: Factors modulating angiogenic responses are dysregulated in patients with IPF with increases in VEGF-A and TSP-1. The serial assessment of VEGF-A and TSP-1 during the follow-up and the search for potential relationships with the outcome of the disease might give us hints to the clinical implication of these results.
    Pathologie Biologie 09/2014; 62(6). DOI:10.1016/j.patbio.2014.07.006 · 1.20 Impact Factor
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