Home About us Contact
|
Home About us Contact | ||
|
|
||
Angiogenic Activity (angiogenic + activity)
Selected AbstractsRetinal Endothelial Angiogenic Activity: Effects of Hypoxia and Glial (Müller) CellsMICROCIRCULATION, Issue 7 2004YOUSEF YAFAI ABSTRACT Objective: To explore the impact of retinal glial (Müller) cells on survival and neovascularization-related activities of cultured retinal endothelial cells under normoxic and hypoxic conditions. Methods: Bovine retinal endothelial cells (BRECs) were cultured under normoxia or hypoxia (0.5% O2) either alone, together with the human Müller cell line MIO-M1, or in normoxia- or hypoxia-conditioned media of MIO-M1 cells. Cell number, proliferation, apoptotic cell death, and migration of BRECs were determined. Results: Exposure of BRECs to hypoxia for 24 h decreased the number of adherent cells and the proliferation rate, but increased apoptosis and cell migration. Increased apoptosis and decreased proliferation of the BRECs occurred also in the presence of conditioned media of MIO-M1 cells. Under normoxic conditions, co-culture with MIO-M1 cells resulted in increased proliferation, but decreased apoptosis and migration rates of BRECs. Under hypoxic conditions, the Müller cells released elevated amounts of VEGF but their presence decreased proliferation, apoptosis and the migration rates of BRECs. Conclusions: Hypoxia inhibits the proliferation of retinal endothelial cells. Müller cells release soluble mediators that enhance this hypoxia-mediated effect but, under certain conditions (i.e., in co-culture), may protect retinal endothelial cells from apoptosis, thus supporting their survival. Altogether the findings indicate that the key signal necessary to trigger retinal endothelial proliferation under hypoxia remains to be determined. [source] Angiogenic activity of multiple myeloma endothelial cells in vivo in the chick embryo chorioallantoic membrane assay is associated to a down-regulation in the expression of endogenous endostatinJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2008Domenica Mangieri Abstract We have attempted a fine characterization of the angiogenic response induced by multiple myeloma endothelial cells (MMEC) by using the chick embryo chorioallantoic membrane (CAM) assay and by reverse transcriptase-polymerase chain reaction (RT-PCR). Results showed that in the CAM assay MMEC induced an angiogenic response comparable to that of a well-known angiogenic cytokine, namely fibroblast growth factor-2 (FGF-2), while RT-PCR demonstrated that the expression of endostatin mRNA detected in MM treated CAM was significantly lower respect to control CAM. These data suggest that angiogenic switch in MM may involve loss of an endogenous angiogenesis inhibitor, such as endostatin. [source] ABH and Lewis histo-blood group antigens in cancerAPMIS, Issue 1 2001JACQUES LE PENDU Antigens of the ABH and Lewis histo-blood group family can be found on many normal cells, mainly of epithelial type. In carcinomas, altered expression of the various carbohydrate epitopes of this family occur, and are often strongly associated with either a good or bad prognosis. A review of the available data on these tumor-associated markers, their biosynthesis and their prognostic value is proposed here. For a long time it has been unclear whether their presence could affect the behavior of carcinoma cells. Recent data, however, indicate that they play biological roles in the course of tumor progression. The presence of sialyl-Lea or sialyl-Lex, which are ligands for selectins, promotes the metastatic process by facilitating interaction with the endothelium of distant organs. The loss of A and B antigens increases cellular motility, while the presence of H epitopes increases resistance to apoptosis by mechanisms that remain to be defined. The Ley antigen has procoagulant and angiogenic activities. All these observations are used to present a model that may account for the described associations between the presence or loss of these markers and the outcome of disease. Finally, their potential clinical applicaitons as tumor-associated markers or as targets of immunotherapy are reviewed. [source] Vascular alterations in the rabbit patellar tendon after surgical incisionJOURNAL OF ANATOMY, Issue 5 2001M. R. DOSCHAK Open incision of the patellar tendon (PT) is thought to promote acute vascular responses which ultimately result in an enhanced degree of tendon repair. Such a clinical procedure is commonly applied to patients with refractory tendinitis. The objective of this study was to quantify the vascular adaptations (both anatomical and physiological) to longitudinal incision of the PT, and the resultant effects on tendon organisation. Fifty-four New Zealand White rabbits were separated into 3 experimental groups and 2 control groups. Experimental groups underwent surgical incision of the right PT, and were assessed 3 d, 10 d and 42 d following injury; normal unoperated controls were evaluated at time zero, and sham-operated controls were evaluated at 3 d to control for the effects of incising the overlying skin. Quantitative measures of PT blood supply (blood flow, microvascular volume) and geometric properties of PT substance were obtained for each PT. Histomorphology was assessed to evaluate vascular remodelling and matrix organisation in the healing PT. Longitudinal open incision surgery of the PT led to rapid increases in both blood flow and vascular volume. The incision of overlying tissues alone (sham-operated) contributed to this measurable increase, and accounted for 36% and 42% of the elevated blood flow and vascular volume respectively at the 3 d interval. In the incised PT, blood flow significantly increased by 3 d compared with both time zero and sham-operated controls, and remained significantly elevated at the 10 d interval. Similarly, vascular volume of the incised PT increased at 3 d compared both with time zero and sham-operated controls. At the 10 d interval, the increase in vascular volume was greatest in the central PT substance. By 42 d both blood flow and vascular volume of the incised tendon had diminished, with only blood flow remaining significantly different from controls. In the contralateral limb, a significant neurogenically mediated vasodilation was measured in the contralateral PTs at both early time intervals, but was not seen by the later 42 d interval. With respect to PT geometric properties in the experimental animals, a larger PT results as the tendon matrix and blood vessels remodel. PT cross-sectional area increased rapidly by 3 d to 1·3 times control values, and remained significantly elevated at 42 d postinjury. Morphological assessments demonstrated the disruption of matrix organisation by vascular and soft tissue components associated with the longitudinal incisions. Substantial changes in matrix organisation persisted at 42 d after surgery. These findings suggest that open longitudinal incision of the PT increases the vascular supply to deep tendon early after injury. These changes probably arise through both vasomotor and angiogenic activity in the tissue. Since PT blood flow and vascular volume return towards control levels after 6 wk but structural features remain disorganised, we propose that vascular remodelling is more rapid and complete than matrix remodelling after surgical incision of the PT. [source] Gorham-Stout Syndrome: A Monocyte-Mediated Cytokine Propelled Disease,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2006Silvia Colucci Abstract We studied the biological features and the immunophenotype of a cell culture established from the lesion of soft tissues of a woman affected by Gorham-Stout syndrome. We found that these cells belonged to a monocytic lineage with some characteristics of immature osteoclasts and were able to release large amounts of osteoclastogenic and angiogenic molecules that may contribute to disease progression. Introduction: Gorham-Stout syndrome is a rare disease characterized by osteolysis and proliferation of vascular or lymphatic vessels, with a severe outcome. Its etiology and the identification of the cell types involved are completely unknown. Materials and Methods: A cell culture from a lesion of soft tissues was established, and its behavior in vitro and in immunodeficient mice was studied. We analyzed (1) the cell phenotype by flow cytometry; (2) the adhesive and migratory properties on different substrates; (3) the ability to differentiate into mature osteoclasts; (4) the production of osteclastogenic and angiogenic molecules; (5) the in vivo angiogenic activity of the cells subcutaneously implanted in mouse in a Matrigel plug; and (6) the ability to recapitulate the disease when transplanted in nude mice. Results and Conclusions: The established culture consisted of a morphologically homogeneous cell population belonging to a monocytic lineage having some features of an osteoclast-like cell type. Cells had an invasive phenotype, were angiogenic, and produced osteoclastogenic (IL-6, TGF-,1, IL-1,) and angiogenic (vascular endothelial growth factor-A {VEGF-A}, CXCL-8) molecules when challenged with inflammatory cytokines. Immunodeficient mice injected with these cells did not show any bone lesions or vascular alteration, but had high amounts of circulating human IL-6 and VEGF-A. Cells isolated from a cutaneous lymphangiomatosis did not show any of these findings. These data suggest that cells of monocyte-macrophage lineage play an essential role in the pathogenesis of Gorham-Stout disease, whose progression is propelled by cytokine circuits that accelerate angiogenesis and osteoclastogenesis. [source] Prognostic value of serum angiogenic activity in colorectal cancer patientsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2007Francisco-Jesus Gonzalez Abstract Angiogenesis, resulting from an imbalance between angiogenic activator factors and inhibitors, is required for tumour growth and metastasis. The determination of the circulating concentration of all angiogenic factors (activators and inhibitors) is not feasible at present. We have evaluated diagnostic and prognostic values of the measurement of serum angiogenic activity in colorectal carcinoma (CRC) patients. Serum proliferative activity (PA) on human umbilical vein endothelial cells (HUVEC) in vitro, and serum vascular endothelial growth factor (VEGF) levels were determined by ELISA in 53 patients with primary CRC, 16 subjects with non-neoplastic gastrointestinal disease (SC) and 34 healthy individuals. Data were compared with clinical outcome of the patients. Although serum from CRC patients significantly increased the PA of HUVEC, compared to culture control (HUVEC in medium + 10% foetal bovine serum (FBS); P < 0.001); our results indicate that serum PA in CRC patients was similar to that of SC or healthy individuals. There was no correlation between serum PA and circulating VEGF concentrations. Surgery produced a decrease of PA at 8 hrs after tumour resection in CRC patients compared to pre-surgery values (186 ± 47 versus 213 ± 41, P < 0.001). However, an increase in serum VEGF values was observed after surgery (280 [176,450] versus 251 [160,357] pg/ml, P = 0.004). Patients with lower PA values after surgery showed a worse outcome that those with higher PA values. Therefore, this study does not support a diagnostic value for serum angiogenic activity measured by proliferative activity on HUVEC but suggests it could have a prognostic value in CRC patients. [source] Nicotinamide phosphoribosyltransferase imparts human endothelial cells with extended replicative lifespan and enhanced angiogenic capacity in a high glucose environmentAGING CELL, Issue 2 2009Nica M. Borradaile Summary Endothelial dysfunction is a characteristic of aging-related vascular disease and is worsened during diabetes. High glucose can impair endothelial cell (EC) function through cellular accumulation of reactive oxygen species, an insult that can also limit replicative lifespan. Nicotinamide phosphoribosyltransferase (Nampt), also known as PBEF and visfatin, is rate-limiting for NAD+ salvage from nicotinamide and confers resistance to oxidative stress via SIRT1. We therefore sought to determine if Nampt expression could resist the detrimental effects of high glucose and confer a survival advantage to human vascular EC in this pathologic environment. Human aortic EC were infected with retrovirus encoding eGFP or eGFP-Nampt, and FACS-selected to yield populations with similar, modest transgene expression. Using a chronic glucose exposure model we tracked EC populations to senescence, assessed cellular metabolism, and determined in vitro angiogenic function. Overexpression of Nampt increased proliferation and extended replicative lifespan, and did so preferentially during glucose overload. Nampt expression delayed markers of senescence and limited reactive oxygen species accumulation in high glucose through a modest increase in aerobic glycolysis. Furthermore, tube networks formed by Nampt-overexpressing EC were more extensive and glucose-resistant, in accordance with SIRT1-mediated repression of the anti-angiogenic transcription factor, FoxO1. We conclude that Nampt enables proliferating human EC to resist the oxidative stress of aging and of high glucose, and to productively use excess glucose to support replicative longevity and angiogenic activity. Enhancing endothelial Nampt activity may thus be beneficial in scenarios requiring EC-based vascular repair and regeneration during aging and hyperglycemia, such as atherosclerosis and diabetes-related vascular disease. [source] TNF-,,induced NF-,B signaling reverses age-related declines in VEGF induction and angiogenic activity in intervertebral disc tissuesJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2009Tetsuro Ohba Abstract We previously demonstrated that VEGF and its receptors were expressed in human herniated discs (HD). TNF-, induced VEGF, resulting in neovascularization of disc tissues in a model of HD. The goal of the current research was to investigate the precise role of TNF-,,induced VEGF and the mechanism of angiogenesis in disc tissues. We performed ELISAs, Western blots, and immunohistological examinations to assess the role of TNF-,,induced VEGF using organ disc cultures with wild type, TNF receptor 1-null (TNF-RInull), or TNF receptor 2-null (TNF-RIInull) mice. VEGF induction was inhibited when we used TNF-RInull -derived disc tissues. NF-,B pathway inhibitors also strongly suppressed VEGF induction. Thus, TNF-, induced VEGF expression in disc cells primarily through the NF-,B pathway. In addition, VEGF immunoreactivity was detected predominantly in annulus fibrosus cells and increased after TNF-, stimulation. TNF-, treatment also resulted in CD31 expression on endothelial cells and formation of an anastomosing network. In contrast, angiogenic activity was strongly inhibited in the presence of NF-,B inhibitors or anti-VEGF antibody. Our data show angiogenesis activity in disc tissues is regulated by VEGF and the NF-,B pathway, both of which are induced by TNF-,. The level of angiogenic activity in disc tissues was closely related to aging. Because neovascularization of HD is indispensable for HD resorption, the prognosis of HD and the rate of the resorption process in patients may vary as a function of the patient's age. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:229,235, 2009 [source] PAR-1 activation has different effects on the angiogenic activity of endothelial progenitor cells derived from human adult and cord bloodJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2006D. M. SMADJA [source] Fas-mediated upregulation of vascular endothelial growth factor and monocyte chemoattractant protein-1 expression in cultured dermal fibroblasts: Role in the inflammatory responseTHE JOURNAL OF DERMATOLOGY, Issue 2 2007Masao FUJIWARA ABSTRACT The Fas,Fas ligand interaction is the most important pathway in starting apoptosis. In addition, several recent reports have emerged documenting non-apoptotic roles for Fas. However, a non-apoptotic role of Fas in dermal fibroblasts remains unknown. The present study investigated whether Fas stimulation not only promotes apoptosis but also stimulates elements of the inflammatory response such as angiogenesis and macrophage infiltration. Fas stimulation was performed by treating cultured human dermal fibroblasts with an agonistic anti-Fas monoclonal antibody (mAb). Anti-Fas mAb-treated fibroblasts showed a significantly greater increase of caspase-3 and caspase-8 activity compared with control fibroblasts. Addition of the anti-Fas mAb induced DNA fragmentation, as confirmed by the DNA ladder assay. Terminal deoxynucleotidyl transferase-mediated 2,-deoxyuridine 5,-triphosphate nick end labeling (TUNEL) staining showed that treatment with the anti-Fas mAb induced an increase of apoptotic fibroblasts in a time-dependent manner. At both mRNA and protein levels, anti-Fas mAb-treated fibroblasts showed significantly higher expression of vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein (MCP)-1 compared with control fibroblasts. A pan-caspase inhibitor (Z-VAD-FMK) significantly inhibited VEGF and MCP-1 expression. After transplantation of fibroblasts into mice with severe combined immunodeficiency, the nodules derived from anti-Fas mAb-treated fibroblasts showed more abundant neovascularization, increased macrophage infiltration, and more apoptotic cells in comparison with nodules derived from control fibroblasts. The results of both in vitro and in vivo studies confirmed significantly higher angiogenic activity and macrophage chemotactic activity of anti-Fas mAb-treated fibroblasts compared with control fibroblasts. [source] Interleukin-6 involvement in brain arteriovenous malformationsANNALS OF NEUROLOGY, Issue 1 2006Yongmei Chen MD We recently reported that the GG genotype of the interleukin-6 (IL-6),174G>C promoter polymorphism is associated with clinical presentation of intracranial hemorrhage in brain arteriovenous malformation (AVM) patients. In this study, we investigated whether tissue IL-6 expression was associated with IL-6,174G>C genotype, and whether IL-6 was linked to downstream targets involved in angiogenesis and vascular instability. Our results showed that the highest IL-6 protein levels in brain AVM tissue were associated with IL-6,174GG genotype (GG: 57.7 ± 20.2; GC: 35.6 ± 26.6; CC: 13.9 ± 10.2pg/mg; p = 0.001). IL-6 protein levels were increased in AVM tissue from patients with hemorrhagic presentation compared with patients without hemorrhage (55 ± 22 vs 40 ± 27pg/mg; p = 0.038). IL-6 messenger RNA expression strongly correlated with messenger RNA levels of IL-1,, tumor necrosis factor-,, IL-8, matrix metalloproteinase-3 (MMP-3), MMP-9, and MMP-12. We further investigated the plausibility of IL-6 being an upstream cytokine responsible for initiating the angiogenic cascade by cell culture and animal experiments. IL-6 induced MMP-3 and MMP-9 expression and activity in mouse brain and increased proliferation and migration of cerebral endothelial cells. Together, our results suggest that the IL-6 genotype associated with intracranial hemorrhage modulates IL-6 expression in brain AVM tissue, which is consistent with the hypothesis that inflammatory processes induce angiogenic activity possibly contributory to brain AVM intracranial hemorrhage. Ann Neurol 2005 [source] | |||||||||||||