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Pathological Angiogenesis (pathological + angiogenesi)
Selected AbstractsCholinergic modulation of angiogenesis: Role of the 7 nicotinic acetylcholine receptorJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2009Jenny C.F. Wu Abstract Pathological angiogenesis contributes to tobacco-related diseases such as malignancy, atherosclerosis and age-related macular degeneration. Nicotine acts on endothelial nicotinic acetylcholine receptors (nAChRs) to activate endothelial cells and to augment pathological angiogenesis. In the current study, we studied nAChR subunits involved in these actions. We detected mRNA for all mammalian nAChR subunits except ,2, ,4, ,, and , in four different types of ECs. Using siRNA methodology, we found that the ,7 nAChR plays a dominant role in nicotine-induced cell signaling (assessed by intracellular calcium and NO imaging, and studies of protein expression and phosphorylation), as well as nicotine-activated EC functions (proliferation, survival, migration, and tube formation). The ,9 and ,7 nAChRs have opposing effects on nicotine-induced cell proliferation and survival. Our studies reveal a critical role for the ,7 nAChR in mediating the effects of nicotine on the endothelium. Other subunits play a modulatory role. These findings may have therapeutic implications for diseases characterized by pathological angiogenesis. J. Cell. Biochem. 108: 433,446, 2009. © 2009 Wiley-Liss, Inc. [source] Angiogenesis and Interstitial Pressure in a Rat Tumour ModelANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2005H. Hünigen Introduction and Aim:, Angiogenesis, the formation of new blood vessels, is a crucial process in physiological and pathological growth. Pathological angiogenesis is responsible for growth and metastasis of solid tumours, and, when blocked, improves prognosis. As a result of the angiogenic cascade in solid tumours an irregular, leaky capillary network develops. The aim of the present study was to define malignant tumours' vascular characteristics and reveal functional anatomy by quantification of the microvasculature and interstitial pressure (IP) in relation to tumour fluid dynamics as visualized by contrast enhanced magnetic resonance imaging (MRI). Material and Methods:, Dynamic MRI and measurement of the IP was performed in 21 rats implanted with colon carcinomas subcutaneously. Angiogenesis was studied by morphometry of the capillaries, and immunolocalization of the angiogenic factor VEGF and VEGF-Receptor 2. Results and Conclusions:, Histology, immunohistochemistry and MRI confirmed concentric arrangement of 4 tumour zones. The tumour margin included loose connective tissue with abundant mononuclear cells. Many large microvessels were seen in this most intensely vascularized zone. IP measurement in this zone was adjusted to the zero level. Diameter of the peripheral zone of vital cells measured 1.3 mm. Capillaries were smaller and sparse. Dynamic MRI revealed peripheral washout of the contrast agent in this zone. After an initial increase of the signal intensity a hypo-intense rim was formed within a few minutes. The intermediate region was characterized by islands of vital tumour cells containing 3% capillaries (hot spots). The innermost area, the necrotic zone, took 35% of the total tumour area with less than 0.5% vessels. The IP increased from the periphery to the centre. VEGF and VEGF-receptor 2 was found in the vessels of the tumour margin and vital tumour cells of the peripheral zone. From this can be concluded that the peripheral washout phenomenon seems to be correlated with elevated interstitial pressure and increased capillary density and therefore may be a reliable sign of malignancy. [source] Increased levels of monokine induced by interferon-, (Mig) in the vitreous of patients with diabetic retinopathyDIABETIC MEDICINE, Issue 7 2008Y. Wakabayashi Abstract Aim To determine the intravitreous concentration of monokine induced by interferon-, (Mig) in patients with diabetic retinopathy (DR) and the relation between Mig and vascular endothelial growth factor (VEGF). Research design and methods Vitreous samples were obtained at the time of vitrectomy from 41 eyes of 38 DR patients (30 with active DR and 11 with inactive DR) and from 15 eyes of 15 non-diabetic patients who had macular disease (control subjects). Human Mig and VEGF were quantified using a FACS Caliber® flow cytometer. Results The vitreous concentration of Mig was increased significantly in patients with both active and inactive DR [148.0 (31.6,997.2; median range) and 82.3 (25.7,347.7) pg/ml, respectively] compared with control subjects [21.0 (5.2,74.3) pg/ml; P < 0.0001 and P < 0.001, respectively]. In DR patients, a significant (P < 0.01) correlation was observed between vitreous concentrations of Mig and VEGF. Conclusion Our results suggest that Mig may play an important role in the pathogenesis of DR and works in consort with VEGF in the progression of pathological angiogenesis in DR. [source] Neovascularization and mast cells with tryptase activity increase simultaneously in human pterygiumJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2007Domenico Ribatti Abstract Mast cells (MC) have been implicated in both normal and pathological angiogenesis, such as that in chronic inflammatory diseases and tumors. This assumption is partially supported by the close structural association between MC and blood vessels and the recruitment of these cells during tumor growth. MC release a number of angiogenic factors among which tryptase, a serine protease stored in MC granules, is one of the most active. In this study, we correlate the extent of angiogenesis with the number of tryptase-reactive MC in tissue fragments from pterygium and normal bulbar conjunctiva investigated by immunohistochemistry, using two murine monoclonal antibodies against the endothelial cell marker CD31 and the MC marker tryptase. Angiogenesis, measured as microvessel density, was highly correlated with MC tryptase-positive cell count in pterygium tissues. These results suggest that the characteristic neovascularization observed in pterygium may be sustained, at least in part, by MC angiogenic mediators, in particular tryptase. [source] Cholinergic modulation of angiogenesis: Role of the 7 nicotinic acetylcholine receptorJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2009Jenny C.F. Wu Abstract Pathological angiogenesis contributes to tobacco-related diseases such as malignancy, atherosclerosis and age-related macular degeneration. Nicotine acts on endothelial nicotinic acetylcholine receptors (nAChRs) to activate endothelial cells and to augment pathological angiogenesis. In the current study, we studied nAChR subunits involved in these actions. We detected mRNA for all mammalian nAChR subunits except ,2, ,4, ,, and , in four different types of ECs. Using siRNA methodology, we found that the ,7 nAChR plays a dominant role in nicotine-induced cell signaling (assessed by intracellular calcium and NO imaging, and studies of protein expression and phosphorylation), as well as nicotine-activated EC functions (proliferation, survival, migration, and tube formation). The ,9 and ,7 nAChRs have opposing effects on nicotine-induced cell proliferation and survival. Our studies reveal a critical role for the ,7 nAChR in mediating the effects of nicotine on the endothelium. Other subunits play a modulatory role. These findings may have therapeutic implications for diseases characterized by pathological angiogenesis. J. Cell. Biochem. 108: 433,446, 2009. © 2009 Wiley-Liss, Inc. [source] Preparation of extracellular domain 3 of human VEGF receptor-2 and the monitoring of its real-time binding to VEGF by biosensorsBIOTECHNOLOGY PROGRESS, Issue 6 2009Juan Zhang Abstract Vascular endothelial growth factor receptor-2 (VEGFR-2) plays an important role in stimulating the proliferation of endothelial cells and improving the permeability of blood vessels, which is involved in tumor angiogenesis, a process that is essential for tumor growth and metastasis. In this study, we describe a method for high yield of recombinant extracellular domain 3 (KDR3) of human VEGFR-2 in an Escherichia coli system with further purification by cation exchange chromatography and immobilized metal affinity chromatography (IMAC). The biological activity of recombinant KDR3 was performed by sequestering VEGF in HUVEC proliferation assay. The real-time binding of human VEGF to immobilized KDR3 was monitored by a label-free biosensor, Optical waveguide lightmode spectroscopy (OWLS). Under the given experimental conditions, the association rate constant ka was 4.2 × 103 M,1 s,1 and the dissociation rate kd was 5.1 × 10,3 s,1. The dissociation constant KD was then calculated to be 1.2 × 10,6 M. The obtained values will serve as baseline parameters for the design of improved versions of recombinant soluble VEGF receptors and the evaluation of developed anti-KDR antibodies. In addition, such a scenario established by the use of OWLS will potentiate the kinetic study of ligand/receptor and antigen/antibody. The receptor discussed here, which block VEGF binding to cell membrane KDR, have potential clinical application in the treatment of cancer and other diseases where pathological angiogenesis is involved. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] 2266: Role of VEGF-isoforms in pathological choroidal angiogenesisACTA OPHTHALMOLOGICA, Issue 2010S VAN DE VEIRE Purpose The aim of this project is to study the specific role of the VEGF-isoforms in pathological angiogenesis, and to investigate the effect of blocking a single isoform on the formation of choroidal neovascularization (CNV). Methods Endothelial and fibroblast cell cultures were made; VEGF 12, 164 or 189 was added to study their effects. VEGF-isoform specific mice (VEGF 120/+, VEGF 164/164 and VEGF188/188 mice) , as well as double transgenic mice (VEGF 120/164, VEGF 164/188 and VEGF120/188 mice) are used to study the role of VEGF-isoforms in pathological angiogenesis. At first, these VEGF-isoform specific mice were backcrossed to a C75Bl/6 background. CNV was induced by placing 3 laser spots at the 9, 12 and 3 o'clock position (100µm spot size, 0.05 s spot duration and 400mW power). Quantification of the area of newly formed blood vessels was determined by retrobulbar dextran linked FITC perfusion. Results Preliminary data in endothelial cell and fibroblast cultures in vitro show that the VEGF121 and VEGF165 isoforms significantly the amount of angiogenesis, whereas the VEGF121 and VEGF189 isoforms play a role in fibrosis. In vivo, the same effects were checked on a fluorescent CD31 and Vimentin immunostaining of the choroids. An inhibition in neovascularization was present in all 3 isoform specific mice, but the effects were comparable. For the moment, mice colonies are being enlarged to repeat experiments and subsequently, these mice are intercrossed to obtain double transgenic mice. Conclusion This study will shed new light on the different role and the inhibition of the VEGF-isoforms in CNV formation during AMD. Thus, our project may open new perspectives for the treatment of various retinopathies that are known to be associated with VEGF upregulation. 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