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The molecular and cellular events in angiogenesis have been elucidated, and defects in this process are present in chronic wounds. Based on this knowledge, new wound healing strategies are emerging to deliver growth factors to the wound bed. Surgeons and other wound-care specialists can use this knowledge to identify defects and select interventions that may promote improved wound granulation and healing. Angiogenesis therapies. Concepts, clinical trials, and considerations for new drug development. The new angiotherapy. Totowa: Humana Press; Clinical applications of research on angiogenesis.

N Engl J Med ; Free radicals and antioxidants in normal physiological functions and human disease.

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Int J Biochem Cell Biol ; Regulation of endometrial angiogenesis. Climacteric ; Angiogenesis in wound healing. J Investig Dermatol Symp Proc ; Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization: a new surrogate marker of atherosclerosis? Vasc Med ; Harrison's Textbook of Internal Medicine. New York: McGraw-Hill; Control of apoptosis during angiogenesis by survivin expression in endothelial cells.

Am J Pathol ; Wound repair.

Synergistic control of cell adhesion by integrins and syndecans. Nat Rev Mol Cell Biol ; Signal transduction to hypoxia-inducible factor 1. Biochem Pharmacol ; Cyclo-oxygenase-2 enhances basic fibroblast growth factor-induced angiogenesis through induction of vascular endothelial growth factor in rat sponge implants. Br J Pharmacol ; Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med ; Perfusion CT for the assessment of tumour vascularity: which protocol? Hallmarks of cancer: the next generation. Cell ; Plasminogen-mediated activation and release of hepatocyte growth factor from extracellular matrix.

On the mechanism of thrombin-induced angiogenesis. Potentiation of vascular endothelial growth factor activity on endothelial cells by up-regulation of its receptors. J Biol Chem ; Human endothelial gelatinases and angiogenesis. PDGF and vessel maturation. Recent Results Cancer Res ; Trophic effects of platelets on cultured endothelial cells are mediated by platelet-associated fibroblast growth factor-2 FGF-2 and vascular endothelial growth factor VEGF.

Thromb Haemost ; Thrombin induces the release of angiopoietin-1 from platelets. An insight into the possibilities of fibroblast growth factor in periodontal regeneration. J Indian Soc Periodontol ; Involvement of macrophage chemotactic protein-1 and interleukin-1beta during inflammatory but not basic fibroblast growth factor-dependent neovascularization in the mouse cornea.

Lab Invest ; Blockade of neoangiogenesis, a new and promising technique to control the growth of malignant tumors and their metastases. Curr Vasc Pharmacol ; Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat Biotechnol ; Fibrin fragment E stimulates the proliferation, migration and differentiation of human microvascular endothelial cells in vitro. Angiogenesis ; Inflammation modulates expression of laminin in the central nervous system following ischemic injury.

J Neuroinflammation ; Role of hypoxia in tumor angiogenesis-molecular and cellular angiogenic crosstalk. Cell Tissue Res ; Inhibition of inducible nitric oxide synthase results in reductions in wound vascular endothelial growth factor expression, granulation tissue formation, and local perfusion. Surgery ; J Endod ; Intermedin is a new angiogenic growth factor.

Blood ; Blood vessel maturation in a 3-dimensional spheroidal coculture model: direct contact with smooth muscle cells regulates endothelial cell quiescence and abrogates VEGF responsiveness. Angiogenesis, vascular endothelial growth factor and its receptors in human surgical wounds. Br J Surg ; Epidermal hyperplasia overlying human melanoma correlates with tumour depth and angiogenesis.

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Melanoma Res ; Topical vascular endothelial growth factor reverses delayed wound healing secondary to angiogenesis inhibitor administration. Wound Repair Regen ; The angiogenesis inhibitor vasostatin does not impair wound healing at tumor-inhibiting doses. J Invest Dermatol ; Surgery and angiogenesis. Biochim Biophys Acta ; Growth factors and cytokines in wound healing. Generation of a specific immunological response to FGF-2 does not affect wound healing or reproduction.

Immunopharmacol Immunotoxicol ; Vascular permeability, vascular hyperpermeability and angiogenesis. Int J Cancer ; Vascular endothelial growth factor increases Rana vascular permeability and compliance by different signalling pathways.

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J Physiol ; Placenta growth factor is induced in human keratinocytes during wound healing. Vascular endothelial growth factor expression, angiogenesis, and necrosis in renal cell carcinomas. Virchows Arch ; Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family.

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Increased expression of alpha6 integrin in endothelial cells unveils a proangiogenic role for basement membrane. Cancer Res ; Loss of methyl-CpG-binding domain protein 2 enhances endothelial angiogenesis and protects mice against hind-limb ischemic injury. Circulation ; Extracellular regulation of TGF-beta activity in wound repair: growth factor latency as a sensor mechanism for injury.

Anti-Angiogenesis - Antiangiogenesis

Transforming growth factor-beta and fibrosis. World J Gastroenterol ; Angiopoietins in angiogenesis and beyond. Expert Opin Investig Drugs ; Apoptosis of human endothelial cells is accompanied by proteolytic processing of latent TGF-beta binding proteins and activation of TGF-beta. Cell Death Differ ; Mast cell tryptase and photoaging: possible involvement in the degradation of extra cellular matrix and basement membrane proteins.

Arch Dermatol Res ; Suppl 1:S Abnormal angiogenesis in diabetes mellitus. Med Res Rev ; Wound-healing protocols for diabetic foot and pressure ulcers. Surg TechnolInt ; Inhibition of lipid peroxidation restores impaired vascular endothelial growth factor expression and stimulates wound healing and angiogenesis in the genetically diabetic mouse. Diabetes ; Effects of steroids and retinoids on wound healing. Arch Surg ; Gene expression and release of growth factors during delayed wound healing: a review of studies in diabetic animals and possible combined laser phototherapy and growth factor treatment to enhance healing.

Photomed Laser Surg ; Adv Wound Care New Rochelle ; Wound healing in haemophilia--breaking the vicious cycle. Haemophilia ;16 Suppl Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. Vascular endothelial growth factor is more important than basic fibroblastic growth factor during ischemic wound healing.

Antibody neutralization of vascular endothelial growth factor inhibits wound granulation tissue formation. J Surg Res ; Cellular dysfunction in the diabetic fibroblast: impairment in migration, vascular endothelial growth factor production, and response to hypoxia. Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. Low-intensity vibration improves angiogenesis and wound healing in diabetic mice.

PLoS One ;9:e Microangiopathy of cutaneous blood and lymphatic capillaries in chronic venous insufficiency CVI.

Angiogenesis Inhibitors in Prostate Cancer Therapy - Eun-mi Yu - Discovery Medicine

Yale J Biol Med ; Microcirculatory dysfunction in chronic venous insufficiency CVI. Microcirculation ;7:S Plasma VEGF as a marker of therapy in patients with chronic venous disease treated with oral micronised flavonoid fraction - a pilot study. Eur J Vasc Endovasc Surg ; Oxygen diffusion in chronic venous ulceration. J Cardiovasc Surg Torino ; Dermal pericapillary fibrin in venous disease and venous ulceration. Arch Dermatol ; Epithelial tissue-type plasminogen activator expression, unlike that of urokinase, its receptor, and plasminogen activator inhibitor-1, is increased in chronic venous ulcers.

Br J Dermatol ; Extravasation of macromolecules and possible trapping of transforming growth factor-beta in venous ulceration. Venous ulcers: pathophysiology and treatment options. Ostomy Wound Manage ; Micronised purified flavonoid fraction: a review of its use in chronic venous insufficiency, venous ulcers and haemorrhoids. Drugs ; Basic fibroblast growth factor bFGF and vascular endothelial growth factor VEGF have been well documented as angiogenic activators [6] , [7] , [8].

While VEGF is a primary mediator of angiogenic responses, bFGF is also one of potent angiogenesis inducers to stimulate the vascular endothelial mitogenesis and is often involved in pathologic angiogenesis. Tumor angiogenesis involves complex and multiple vascular endothelial responses as well as contributions from tumor cells. The endothelial responses include angiogenic factor-stimulated changes in the vascular endothelial permeability, degradation of the basement membrane by metalloproteases, migration, remodeling and proliferation of endothelial cells to form capillary tubes, and other processes.

On the other hand, tumor cells or host stromal cells express VEGF induced by hypoxia and other autocrine or paracrine growth factors [2] , [3] , [4] , [6] , [7] , [8] , [9] to stimulate endothelial progenitor cells for angiogenesis. Interruptions of one or more steps in these processes can negatively affect angiogenesis and inhibit early malignant lesions to lower the cancer risk [10] VEGF expression is mediated by the phosphoinositide 3-kinase PI3K pathway in endothelial cells [11].

Also, PI3K pathway reveals its effects through its downstream kinase AKT to regulate various cellular processes including angiogenesis [12].

Angiogenesis inhibition

Paeonol oxime 1-[2-hydroxymethoxy phenyl] ethanone oxime; PO was derived from paeonol 2-hydroxy, 4-methoxy acetophenone , which has been shown to be anti-angiogenic [13] Fig. We designed and synthesized PO so that it also shares some similarity with acetylsalicylic acid Fig. We also explored the potential signaling events affected by PO in angiogenic HT cells by Western blotting and immunofluorescence microscopy.

Paeonol oxime PO 1-[2-hydroxymethoxy phenyl] ethanone oxime was synthesized from paeonol.