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Results for “Neovascularization, Pathologic”

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At least 19 recordsLinked to original sources
PubMed1996

Nitric oxide mediates interleukin-1-induced matrix degradation and basic fibroblast growth factor release in cultured rabbit articular chondrocytes: a possible mechanism of pathological neovascularization in arthritis.

Prolonged incubation with interleukin-1 beta (IL-1) induced the release of large amounts of NO and subsequently inhibited DNA synthesis and the biosynthesis and accumulation of proteoglycans in cultured rabbit articular chondrocytes (RAC). IL-1 also inhibited DNA synthesis in bovine aortic endothelial cells (BAE). On the other hand, DNA synthesis in BAE cocultured with RAC was not inhibited by prolonged incubation with IL-1. Moreover, conditioned media from RAC incubated for a long period with IL-1 stimulated DNA synthesis in BAE alone. This growth stimulatory activity was mainly due to the release of basic fibroblast growth factor, a heparin-binding growth factor, into RAC culture. Gelatin zymography of the RAC culture medium revealed that IL-1 increased the production of matrix metalloproteinase-2 (MMP-2) and MMP-9. NG-Monomethyl-L-arginine, an inhibitor of NO synthesis, inhibited all of these actions of IL-1. These results indicate that NO from RAC treated with IL-1 stimulates MMPs, which, in turn, degrade the extracellular matrix produced by RAC, resulting in the release of large amounts of basic fibroblast growth factor stored in the matrix, which then stimulates adjacent BAE proliferation. Thus, NO produced from RAC treated with IL-1 may modulate angiogenesis in the synovium of arthritic patients.

Animals↗
PubMed1999

Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization.

Circulating endothelial progenitor cells (EPCs) have been isolated in peripheral blood of adult species. To determine the origin and role of EPCs contributing to postnatal vasculogenesis, transgenic mice constitutively expressing beta-galactosidase under the transcriptional regulation of an endothelial cell-specific promoter (Flk-1/LZ or Tie-2/LZ) were used as transplant donors. Localization of EPCs, indicated by flk-1 or tie-2/lacZ fusion transcripts, were identified in corpus luteal and endometrial neovasculature after inductive ovulation. Mouse syngeneic colon cancer cells (MCA38) were implanted subcutaneously into Flk-1/LZ/BMT (bone marrow transplantation) and Tie-2/LZ/BMT mice; tumor samples harvested at 1 week disclosed abundant flk-1/lacZ and tie-2/lacZ fusion transcripts, and sections stained with X-gal demonstrated that the neovasculature of the developing tumor frequently comprised Flk-1- or Tie-2-expressing EPCs. Cutaneous wounds examined at 4 days and 7 days after skin removal by punch biopsy disclosed EPCs incorporated into foci of neovascularization at high frequency. One week after the onset of hindlimb ischemia, lacZ-positive EPCs were identified incorporated into capillaries among skeletal myocytes. After permanent ligation of the left anterior descending coronary artery, histological samples from sites of myocardial infarction demonstrated incorporation of EPCs into foci of neovascularization at the border of the infarct. These findings indicate that postnatal neovascularization does not rely exclusively on sprouting from preexisting blood vessels (angiogenesis); instead, EPCs circulate from bone marrow to incorporate into and thus contribute to postnatal physiological and pathological neovascularization, which is consistent with postnatal vasculogenesis.

Animals↗
PubMed2005

Inhibition of tumor necrosis factor-alpha improves physiological angiogenesis and reduces pathological neovascularization in ischemic retinopathy.

The present study was undertaken to test whether inhibition of the proangiogenic inflammatory cytokine tumor necrosis factor (TNF)-alpha can modulate retinal hypoxia and preretinal neovascularization in a murine model of oxygen-induced retinopathy (OIR). OIR was produced in TNF-alpha-/- and wild-type (WT) control C57B6 neonatal mice by exposure to 75% oxygen between postnatal days 7 and 12 (P7 to P12). Half of each WT litter was treated with the cytokine inhibitor semapimod (formerly known as CNI-1493) (5 mg/kg) by daily intraperitoneal injection from the time of reintroduction to room air at P12 until P17. The extent of preretinal neovascularization and intraretinal revascularization was quantified by image analysis of retinal flat-mounts and retinal hypoxia correlated with vascularization by immunofluorescent localization of the hypoxia-sensitive drug pimonidazole (hypoxyprobe, HP). HP adducts were also characterized by Western analysis and quantified by competitive enzyme-linked immunosorbent assay. TNF-alpha-/- and WT mice showed a similar sensitivity to hyperoxia-induced retinal ischemia at P12. At P13 some delay in early reperfusion was evident in TNF-alpha-/- and WT mice treated with semapimod. However, at P17 both these groups had significantly better vascular recovery with less ischemic/hypoxic retina and preretinal neovascularization compared to untreated retinopathy in WT mice. Immunohistochemistry showed deposition of HP in the avascular inner retina but not in areas underlying preretinal neovascularization, indicating that such aberrant vasculature can reduce retinal hypoxia. Inhibition of TNF-alpha significantly improves vascular recovery within ischemic tissue and reduces pathological neovascularization in OIR. HP provides a useful tool for mapping and quantifying tissue hypoxia in experimental ischemic retinopathy.

Animals↗
PubMed2002

Pathologic neovascularization in cartilage tumors.

Tumor-induced angiogenesis is necessary to sustain radial growth of tumors. Increased microvascularity has been correlated with increased metastatic potential in breast, gastrointestinal, and gynecologic tumors, but has not been well studied in cartilaginous tumors. Grade II and Grade III chondrosarcomas have increased metastatic potential compared with Grade I tumors. One reason for this may be pathologic neovascularization. The purpose of the current study was to quantify the microvessel density of cartilage tumors. Seven Grade III, 17 Grade II, and eight Grade I chondrosarcomas, and 22 benign cartilage tumors were examined. Specimens were stained with antiCD34 antibody. Microvessel densities then were determined by direct counting and estimated using the Chalkley technique. Microvessel densities for Grade III and Grade II chondrosarcomas were 45.9 and 46.2 per high-power field and for Grade I and benign tumors the microvessel densities were 9.3 and 10.3. Microvessel densities of the aggressive tumors (Grades III and II) were greater than the microvessel densities of the nonaggressive tumors (Grade I and benign). Chalkley estimates confirmed the results. Microvascularity in cartilage tumors correlates with their biologic aggressiveness and seems promising as a variable to help with histopathologic grading and as a target for new treatment modalities.

Bone Neoplasms↗
PubMed2003

[Using thalidomide against pathological neovascularization].

Thalidomide was first used during the 50's-60's, especially for morning sickness in pregnant women. It was found to be a powerful teratogen only years later and was banned from use. At the same time it was found to have anti-inflammatory and anti-angiogenic properties and was approved as treatment for leprosy. As such, thalidomide might be used against pathological neovascularization, as seen in mustard gas exposure. From past experience we know that the eyes are the most vulnerable organ to mustard gas exposure. In some of the casualties there is a late sequella including pathological corneal neovascularization. So far there is no specific effective treatment against this neovascularization. The purpose of this review is to examine current research about the potential use of thalidomide as an anti-angiogenic agent, including potential role in treating mustard gas eye injury.

Angiogenesis Inhibitors↗
PubMed2003

Potential role for ADAM15 in pathological neovascularization in mice.

ADAM15 (named for a disintegrin and metalloprotease 15, metargidin) is a membrane-anchored glycoprotein that has been implicated in cell-cell or cell-matrix interactions and in the proteolysis of molecules on the cell surface or extracellular matrix. To characterize the potential roles of ADAM15 during development and in adult mice, we analyzed its expression pattern by mRNA in situ hybridization and generated mice carrying a targeted deletion of ADAM15 (adam15(-/-) mice). A high level of expression of ADAM15 was found in vascular cells, the endocardium, hypertrophic cells in developing bone, and specific areas of the hippocampus and cerebellum. However, despite the pronounced expression of ADAM15 in these tissues, no major developmental defects or pathological phenotypes were evident in adam15(-/-) mice. The elevated levels of ADAM15 in endothelial cells prompted an evaluation of its role in neovascularization. In a mouse model for retinopathy of prematurity, adam15(-/-) mice had a major reduction in neovascularization compared to wild-type controls. Furthermore, the size of tumors resulting from implanted B16F0 mouse melanoma cells was significantly smaller in adam15(-/-) mice than in wild-type controls. Since ADAM15 does not appear to be required for developmental angiogenesis or for adult homeostasis, it may represent a novel target for the design of inhibitors of pathological neovascularization.

ADAM Proteins↗
PubMed2000

Angiopoietin 2 expression in the retina: upregulation during physiologic and pathologic neovascularization.

Vascular development in the embryo requires coordinated signaling through several endothelial cell-specific receptors; however, it is not known whether this is also required later during retinal vascular development or as part of retinal neovascularization in adults. The Tie2 receptor has been implicated in stabilization and maturation of vessels through action of an agonist ligand, angiopoietin 1 (Ang1) and an antagonistic ligand, Ang2. In this study, we have demonstrated that ang2 mRNA levels are increased in the retina during development of the deep retinal capillaries by angiogenesis and during pathologic angiogenesis in a model of ischemic retinopathy. Mice with hemizygous disruption of the ang2 gene by insertion of a promoterless beta-galactosidase (beta gal) gene behind the ang2 promoter, show constitutive beta gal staining primarily in cells along the outer border of the inner nuclear layer identified as horizontal cells by colocalization of calbindin. During development of the deep capillary bed or retinal neovascularization, other cells in the inner nuclear layer and ganglion cell layer, in regions of neovascularization, stain for beta gal. Thus, there is temporal and spatial correlation of Ang2 expression with developmental and pathologic angiogenesis in the retina, suggesting that it may play a role.

Angiopoietin-1↗
PubMed2005

Transgenic expression of leukemia inhibitory factor (LIF) blocks normal vascular development but not pathological neovascularization in the eye.

PURPOSE: Vascular development in the eye has been described as a complex process involving both vasculogenesis and angiogenesis. Multiple cell types are involved in the process including angioblasts, vascular endothelial cells, astrocytes, pericytes, and Muller glial cells. This suggests that multiple growth factors and cytokines are required to regulate retinal vascular development. Leukemia inhibitory factor (LIF) is a member of the interleukin 6 family of cytokines. LIF is expressed during inflammation and has been reported to affect vascular development in culture; however, its effects in vivo have not been demonstrated. The purpose of this study was to determine how LIF could regulate ocular vascular development. METHODS: We have analyzed ocular vascular development in transgenic mice that express LIF in the ocular lens from embryonic day 11. RESULTS: In transgenic mice, LIF reduced development of embryonic vasculature in the eye, and inhibited retinal vascular development. Inhibition in vivo was independent of vascular endothelial cell growth factor (VEGF) expression. In older transgenic mice, the absence of a retinal vasculature resulted in retinal ischemia and elevated VEGF levels. The upregulation of VEGF resulted in the proliferation of pathological vascular membranes in the vitreous and neovascularization penetrating the retina, which in turn resulted in tractional retinal detachment. CONCLUSIONS: LIF is a potent inhibitor of retinal vascular development. These transgenic mice will be useful as a model of persistent fetal vasculature and to study the mechanism for the development of neovascular membranes in the vitreous and could be used to develop inhibitors of tractional detachment.

Animals↗
PubMed2006

Vascular update: morphogenesis, tumors, malformations, and molecular dimensions.

This vascular review is organized under the following headings: vasculogenesis and angiogenesis; vascular endothelial growth factors, their receptors, TIE receptors, and angiopoietins; other factors in blood vessel formation; parallel patterning in blood vessels and nerves; physiological and pathological neovascularization; the role of VEGF receptors in metastasis; anti-angiogenic therapy for tumors; association of blood vessels with fat; vascular malformations and vascular tumors; infantile hemangiomas; congenital hemangiomas; lymphatic malformations; molecular characteristics of some disorders with vascular malformations; Kasabach-Merritt phenomenon; Sturge-Weber syndrome, Klippel-Trenaunay syndrome, and Parkes Weber syndrome; diagnostic and laboratory studies; and future perspectives.

Angiogenesis Inhibitors↗
PubMed2006

Expression of the TAL1/SCL transcription factor in physiological and pathological vascular processes.

The TAL1/SCL transcription factor is essential for haematopoietic commitment and vascular remodelling during embryonic development. To help clarify its role in postnatal vascular processes, we characterized the expression of mouse Tal1 protein by immunocytochemistry in several experimental models of blood vessel formation. In adult mice, Tal1 protein was expressed in rare microvascular endothelial cells and in extravascular cells provisionally identified as endothelial progenitors from their morphology, proximity to vessels and expression of vascular endothelial growth factor receptor-2. The number of Tal1-expressing endothelial cells increased significantly but transiently in all the models-hormone-induced ovulation, wound healing and tumour development. Finally, Tal1 protein was detected in the nuclei of newly formed lymphatic endothelial cells in tumour-bearing animals. These results show that TAL1 is expressed by vascular endothelial cells and endothelial progenitors at sites of physiological and pathological neovascularization and suggest a role for this transcription factor in adult vasculogenesis. This work also provides the first evidence for TAL1 expression in lymphangiogenesis.

Animals↗
PubMedDate not supplied

Effects of cytogenin, a novel microbial product, on embryonic and tumor cell-induced angiogenic responses in vivo.

Cytogenin (8-hydroxy-3-hydroxymethyl-6-methoxyisocoumarin) is a new microbial product with antitumor and antirheumatoid arthritis effects in vivo when administered orally, although its mechanism(s) of action is not known well. Both neoplasia and rheumatoid arthritis are referred to as angiogenesis-dependent diseases. The aim of the present study was to investigate the effects of cytogenin on both physiological and pathological angiogenesis, using the growing chick embryo chorioallantoic membrane and mouse dorsal air sac assay systems, respectively. The microbial product at doses up to 100 micrograms/egg did not significantly affect embryonic angiogenesis when topically placed on the surface of the chorioallantoic membrane, suggesting that it has no effect on the physiological (or normal) angiogenic response. By contrast, systemic administration of cytogenin (100 mg/kg p.o., for 5 consecutive days) significantly suppressed angiogenesis induced by malignant tumor cells (S-180), one of pathological neovascularization, in a mouse dorsal air sac assay system. Pharmacokinetic studies in mice revealed that the maximal concentration of cytogenin in plasma after a single 100 mg/kg oral dose of the compound was 32 microM. In vitro experiments involving cultured vascular endothelial cells showed that cytogenin at concentrations determined by pharmacokinetic study, had little effect on plasminogen activator secretion, tube formation and the proliferation of endothelial cells. These results suggest that cytogenin is a novel oral antiangiogenic agent, that the mechanism of its antiangiogenic action contributes to its suppressive effects on both tumor growth and rheumatoid arthritis that we previously found, and that it could be developed as a potential therapeutic agent for cancer, rheumatoid arthritis and other angiogenesis-dependent disorders such as diabetic retinopathy.

Allantois↗
PubMed2001

Inhibition of angiogenesis by adenovirus-mediated sFlt-1 expression in a rat model of corneal neovascularization.

Pathological angiogenesis, or the production of new capillary vessels from preexisting vasculature, within the eye is a serious event that often leads to blindness. Upregulation of vascular endothelial growth factor (VEGF) has been linked to neovascularization in the eye, suggesting that it could be a suitable target to inhibit angiogenic changes. This work investigated whether the presence of a proven antiangiogenic factor, the soluble variant of the VEGF receptor, sFlt-1, in the anterior chamber is sufficient to inhibit new vessel formation in the cornea in an animal model of corneal neovascularization. A recombinant adenovirus vector that can mediate efficient in vivo gene transfer and expression in ocular cells was selected as a delivery agent. We have shown that after the injection of Ad.betagal into the anterior chamber of normal and cauterized rat eyes, corneal endothelial cells and cells of the trabecular meshwork were efficiently transduced and that beta-galactosidase (beta-Gal) expression was maintained up to 10 days postinjection. Cauterization significantly increased the amount of immunoreactive VEGF in vehicle- or Ad.null-injected animals (t test, p < 0.001 and p < 0.001, respectively). However, when cauterization was combined with Ad.sflt injection there was no statistically significant increase in the amount of immunoreactive VEGF (p = 0.12). The injection of Ad.sflt into the anterior chamber slowed or inhibited VEGF-induced angiogenic changes. After cauterization, 100% of uninjected and vehicle-injected and 82% of Ad.null-injected animals developed moderate to severe corneal angiogenesis in contrast to 18% of Ad.sflt-injected animals. These in vivo results suggest that the transient presence of antiangiogenic agents in the anterior chamber can be successfully used to inhibit the development of corneal angiogenesis.

Adenoviridae↗
PubMed1993

[Early lesion of choroidal neovascularization. 2. Early lesion of choroidal neovascularization in pathological myopia].

We describe early features of choroidal neovascularization in 50 pathologically myopic eyes. The eyes were classified into three categories on the basis of degree of myopic chorioretinal degeneration in the posterior pole: mild diffuse atrophy, severe diffuse atrophy and focal atrophy. Choroidal neovascular membranes (CNMs) were grouped into a minimally leaking type and a markedly leaking type in fluorescein angiographic patterns. CNMs were more frequently associated with the mild diffuse atrophy than with the other atrophies. Of the markedly leaking CNMs, 83% were seen in eyes with mild myopic chorioretinal degeneration and 78.5% of the minimal leaking CNMs were found in eyes with severe myopic chorioretinal degeneration. In association with CNMs, lacquer crack and the granular hypofluorescein lesions were observed in 72% and 40%, respectively. The visual acuity deteriorated in all of the 14 eyes which could be followed up more than 1 year.

Adult↗
PubMed1988

Dye laser photocoagulation of macular subretinal neovascularization in pathological myopia. A randomized study of three different wavelengths.

The authors present a randomized study of 27 eyes affected by pathological myopia with macular subretinal neovascularization which were treated with a tunable dye laser. The effectiveness of three different wavelengths (577, 590 and 620 nm) in the direct treatment of subretinal neovascularizations was evaluated in 3 groups of 9 patients each. Statistical analysis of both visual and anatomical results did not show significant differences among the three wavelengths used.

Adult↗
PubMedDate not supplied

Laser photocoagulation of choroidal neovascularization in pathologic myopia: long-term results.

Direct laser photocoagulation of macular choroidal neovascularization (CNV) in pathologic myopia is still controversial. However, previous studies have reported encouraging results. One-hundred and thirty-three consecutively treated eyes were followed, in a prospective manner, for at least 12 months (108 of these were followed for 24 months, 84 for 36 months, 63 for 48 months, and 47 for 60 months) to evaluate the potential benefits and complications of laser treatment of extra-foveal macular CNV in pathologically myopic eyes. Pre-treatment mean visual acuity was 0.36. Post-treatment mean visual acuity was 0.33 at 1-year examination, 0.31 at 2 years, 0.32 at 3 years, 0.34 at 4 years, and 0.33 at 5 years. During the total follow-up period mean visual acuity did not change. Neovascular recurrences occurred in 58% of treated eyes by the end of the five-year follow-up. At final examination, complete destruction of CNV was achieved in 100 eyes (75%). These findings suggest that laser photocoagulation of macular choroidal neovascularization in pathologic myopia may be effective in preventing or limiting severe and irreversible loss of vision.

Adult↗
PubMed2004

Prognostic factors influencing visual outcome of photodynamic therapy for subfoveal choroidal neovascularization in pathologic myopia.

PURPOSE: To examine the influence of age, lesion size, degree of myopia, and baseline visual acuity on the visual outcome of patients with pathologic myopia and choroidal neovascularization (CNV) who received photodynamic therapy (PDT) with verteporfin. DESIGN: Retrospective, noncomparative consecutive case series. METHODS: Forty-three eyes of 41 patients were treated in a two-year time span; 36 eyes of 36 patients who had received PDT for CNV due to pathologic myopia were examined for the above-mentioned factors 24 months after first treatment. All patients had been treated according to the Verteporfin in Photodynamic Therapy (VIP) study criteria. Patients were examined in two- to three-month intervals with Snellen visual acuity, biomicroscopy, and fluorescein angiography. RESULTS: Baseline visual acuity and age were both prognostic factors for visual outcome (P =.0097, P =.0055). Lesion size (greatest linear dimension) at baseline, refractive error, or the number of treatments had no influence on the outcome. CONCLUSION: Age and baseline visual acuity have an effect on visual outcome in patients receiving PDT due to CNV secondary to pathologic myopia. Younger patients and patients with higher baseline visual acuity had a better treatment outcome.

Adult↗
PubMed1996

Subretinal bleeding without choroidal neovascularization in pathologic myopia. A sign of new lacquer crack formation.

PURPOSE: The clinical significance of subretinal bleeding without choroidal neovascularization in pathologic myopia is unclear. Only two reports in the ophthalmic literature have demonstrated the clinical course of subretinal bleeding and have indicated that it might be a precursor of lacquer cracks. In this study, the authors observed the clinical course of subretinal bleeding in highly myopic eyes and studied this condition in relation to new lacquer crack formation. METHODS: The authors examined consecutively and prospectively 22 highly myopic eyes (19 patients) with subretinal bleeding. Indirect ophthalmoscopy and fluorescein fundus angiography were performed in all patients. Indocyanine green (ICG) angiography could be performed in three patients. The follow-up period ranged from 6 to 198 months (mean, 61.3 months). RESULTS: In 17 of 22 eyes, lacquer cracks appeared at the site of previous subretinal bleeding. The period for the formation of new lacquer cracks after the onset of the bleeding ranged from 2 to 6 months (mean, 4.0 months). In one patient, ICG angiography revealed linear hypofluorescence, indicating a ruptured Bruch's membrane at the onset of subretinal bleeding. CONCLUSION: A rupture of Bruch's membrane and choriocapillaris complex results in subretinal bleeding, which is the first process of new lacquer crack formation. Atrophy of the overlying pigment epithelium and further scar formation results in the development of a lacquer crack.

Adolescent↗
PubMed1983

Pathological vascularization of the coronary intima.

Secondary vascularization was found in the walls of diseased coronary arteries from 36 individuals who died after sudden cardiac arrest. In the series presented here, coronary arteries of hospital patients dying from all causes also showed a 100% incidence of pathological neovascularization. A process linking neovascularization and chronic inflammation to an ultimate infectious aetiology is suggested.

Adult↗