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Angiogenesis
Kinds of Angiogenesis Terms modified by Angiogenesis Selected AbstractsAngiotensin II regulates endothelial cell migration through calcium influx via T-type calcium channel in human umbilical vein endothelial cellsACTA PHYSIOLOGICA, Issue 4 2010A. Martini Abstract Aim:, The T-type calcium channel is expressed in vascular endothelial cells, but its role in endothelial cell function is yet to be elucidated. We analysed the endothelial functional role of T-type calcium channel-dependent calcium under angiotensin II (Ang II) stimulation. Methods:, Human umbilical vein endothelial cells were co-incubated with hormone at 10,7 m and either Efonidipine 10,5 m or Verapamil 10,5 m or Mibefradil 10,5 m or Wortmannin 10,6 m. The contribution of Ang II receptors was evaluated using PD123319 10,7 m and ZD 7155 10,7 m. The calcium ion concentration was observed using Fluo-3 acetossimetil ester. The cells were observed after 3, 6, 9 and 12 h. Results:, The microfluorescence method points out that Ang II induces intracellular calcium modulation in time by distinct mechanisms. AT2 receptor blockade is necessary to observe significant increase in [Ca2+]i levels. Pre-treatment with Mibefradil abolishes Ang II -induced cell migration. Conclusions:, Our data show that Ang II, via AT1 receptor, modulates calcium concentration involving T-type calcium channel and L-type calcium channel but only the calcium influx via T-type calcium channels regulates endothelial cell migration which is essential for angiogenesis. [source] MR imaging in assessing cardiovascular interventions and myocardial injuryCONTRAST MEDIA & MOLECULAR IMAGING, Issue 1 2007Alexis Jacquier Abstract Performing an MR-guided endovascular intervention requires (1) real-time tracking and guidance of catheters/guide wires to the target, (2) high-resolution images of the target and its surroundings in order to define the extent of the target, (3) performing a therapeutic procedure (delivery of stent or injection of gene or cells) and (4) evaluating the outcome of the therapeutic procedure. The combination of X-ray and MR imaging (XMR) in a single suite was designed for new interventional procedures. MR contrast media can be used to delineate myocardial infarcts and microvascular obstruction, thereby defining the target for local delivery of therapeutic agents under MR-guidance. Iron particles, or gadolinium- or dysprosium-chelates are mixed with the soluble injectates or stem cells in order to track intramyocardial delivery and distribution. Preliminary results show that genes encoded for vascular endothelial and fibroblast growth factor and cells are effective in promoting angiogenesis, arteriogenesis, perfusion and LV function. Angiogenic growth factors, genes and cells administered under MR-guided minimally invasive catheter-based procedures will open up new avenues in treating end-stage ischemic heart disease. The optimum dose of the therapeutic agents, delivery devices and real-time imaging techniques to guide the delivery are currently the subject of ongoing research. The aim of this review is to (1) provide an updated review of experiences using MR imaging to guide transcatheter therapy, (2) address the potential of cardiovascular magnetic resonance (MR) imaging and MR contrast media in assessing myocardial injury at a molecular level and labeling cells and (3) illustrate the applicability of the non-invasive MR imaging in the field of angiogenic therapies through recent clinical and experimental publications. Copyright © 2007 John Wiley & Sons, Ltd. [source] CMR 2005: 3.03: New RGD peptide-based molecular imaging agents for detection of angiogenesisCONTRAST MEDIA & MOLECULAR IMAGING, Issue 2 2006B. Indrevoll [source] Adventures in multivalency, the Harry S. Fischer memorial lecture CMR 2005; Evian, FranceCONTRAST MEDIA & MOLECULAR IMAGING, Issue 1 2006Michael F. Tweedle Abstract This review discusses multivalency in the context of drug discovery, specifically the discovery of new diagnostic imaging and related agents. The aim is to draw attention to the powerful role that multivalency plays throughout research involving molecular biology, in general, and much of biochemically targeted contrast agent research, in particular. Two examples from the author's laboratory are described. We created small (,5,kDa) peptide ,dimers' composed of two different, chemically linked peptides. The monomer peptides both bound to the same target protein with Kd,,,100,s,nM, while the heterodimers had sub-nM Kd values. Biological activity was evident in the heterodimers where none or very little existed in homodimers, monomers or monomer mixtures. Two different tyrosine kinases (KDR and C-Met) and four peptide families produced consistent results: multivalent heterodimers were uniquely different. The second example begins with making two micron ultrasound bubbles coated with the peptide, TKPPR (a Tuftsin antagonist) as a negative control for bubbles targeted with angiogenesis target-binding peptides. Unexpected binding of a ,negative' control, (TKPPR)-targeted bubble to endothelial cells expressing angiogenesis targets, led to the surprising result that TKPPR, only when multimerized, binds avidly, specifically and actively to neuropilin-1, a VEGF co-receptor. VEGF is the primary stimulator of angiogenesis. Tuftsin is a small peptide (TKPR) derived from IgG that binds to macrophages during inflammation, and has been studied for over 30 years. The receptor has never been cloned. The results led to new conclusions about Tuftsin, neuropilin-1 and the purpose, up to now unknown, of exon 8 in VEGF. Multivalency can be used rationally to solve practical problems in drug discovery. When targeting larger structures, multivalency is frequently unavoidable, and can lead to unpredictable and useful biochemical information, as well as to new drug candidates. Copyright © 2006 John Wiley & Sons, Ltd. [source] In vivo functions of the prolyl-4-hydroxylase domain oxygen sensors: direct route to the treatment of anaemia and the protection of ischaemic tissuesACTA PHYSIOLOGICA, Issue 4 2009D. M. Katschinski Abstract The prolyl-4-hydroxylase domain (PHD) 1,3 enzymes have been identified based on their ability to regulate the stability of hypoxia-inducible factor , subunits and thus to modify hypoxia-inducible gene expression. Transgenic mouse models provided insights into the isoform-specific functions of these oxygen sensors with physiological implications for angiogenesis, erythropoiesis/oxygen transport, cardiovascular function, metabolism and tissue homeostasis. This knowledge is important for the ongoing development of small molecule PHD inhibitors that are currently tested in preclinical and clinical trials for the treatment of anaemia and for cytoprotection. This review aims at summarizing the insights obtained from key mouse knock-out models as well as first experiences in the therapeutic application of PHD inhibitors. [source] Development of micropost force sensor array with culture experiments for determination of cell traction forcesCYTOSKELETON, Issue 7 2007Bin Li Abstract Cell traction forces (CTFs) are critical for cell motility and cell shape maintenance. As such, they play a fundamental role in many biological processes such as angiogenesis, embryogenesis, inflammation, and wound healing. To determine CTFs at the sub-cellular level with high sensitivity, we have developed high density micropost force sensor array (MFSA), which consists of an array of vertically standing poly(dimethylsiloxane) (PDMS) microposts, 2 ,m in diameter and 6 ,m in height, with a center-to-center distance of 4 ,m. In combination with new image analysis algorithms, the MFSA can achieve a spatial resolution of 40 nm and a force sensitivity of 0.5 nN. Culture experiments with various types of cells showed that this MFSA technology can effectively determine CTFs of cells with different sizes and traction force magnitudes. Cell Motil. Cytoskeleton 2007. © 2007 Wiley-Liss, Inc. [source] Comparison of acidic fibroblast growth factor on collagen carrier with calcium hydroxide as pulp capping agents in monkeysDENTAL TRAUMATOLOGY, Issue 5 2007Zhimei Li Abstract,,, Acidic fibroblast growth factor (aFGF) has been shown to facilitate wound healing by stimulating fibroblast proliferation and angiogenesis. It has also been reported to possess a powerful anti-apoptotic function This study compared the histological pulp responses to aFGF on collagen carrier and Ca(OH)2 placed on the mechanically exposed dental pulp in monkeys at two observation periods. Thirty-six teeth with pulp exposures were distributed into three groups according to the capping agents used prior to application of the coronal seal: collagen-based matrix carrier (group 1), aFGF on the collagen-based matrix carrier (group 2) and aqueous calcium hydroxide [Ca(OH)2] paste (group 3). Specimens were harvested at 6 and 13 weeks postoperatively and prepared for hematoxylin and eosin, and Gram staining. Histological qualitative evaluation of pulp responses were performed under the light microscope following criteria modified from Cox et al. (17) and Hu et al. (18). Semi-quantitative analysis was also carried out using Kruskal,Wallis and Mann,Whitney U -tests. There was neither negligible inflammatory infiltrates with no bacteria present in the three groups at both timings, nor was there any significant difference in the soft tissue organization among the three groups at or between the 6- and 13-week observation periods. At 6 weeks, the hard tissue barrier produced by Ca(OH)2 group (1.040 ± 0.089) was significantly more superior than aFGF/collagen carrier group (1.930 ± 0.825) (P = 0.030) as well as collagen carrier group (3.142 ± 1.069, P = 0.018). At 13 weeks, both aFGF/collagen carrier group (1.214 ± 0.485) and the collagen carrier group (1.457 ± 0.814) produced significantly better hard tissue barrier (P = 0.040 and P = 0.017, respectively) than earlier timing. However, these two groups did not induce significantly improved hard tissue barrier compared to that produced by aqueous Ca(OH)2 paste which stimulated matrix secretion in a polar tubular dentin-like pattern. [source] In Vivo Perfusion of Human Skin Substitutes With Microvessels Formed by Adult Circulating Endothelial Progenitor CellsDERMATOLOGIC SURGERY, Issue 2 2008ELAINE F. KUNG MD BACKGROUND At present, tissue-engineered human skin substitutes (HSSs) mainly function as temporary bioactive dressings due to inadequate perfusion. Failure to form functional vascular networks within the initial posttransplantation period compromises cell survival of the graft and its long-term viability in the wound bed. OBJECTIVES Our goal was to demonstrate that adult circulating endothelial progenitor cells (EPCs) seeded onto HSS can form functional microvessels capable of graft neovascularization and perfusion. MATERIALS AND METHODS Adult peripheral blood mononuclear cells (PBMCs) underwent CD34 selection and endothelial cell (EC) culture conditions. After in vitro expansion, flow cytometry verified EC phenotype before their incorporation into HSS. After 2 weeks in vivo, immunohistochemical analysis, immunofluorescent microscopy, and microfil polymer perfusion were performed. RESULTS CD34+ PBMCs differentiated into EPC demonstrating characteristic EC morphology and expression of CD31, Tie-2, and E-selectin after TNF,-induction. Numerous human CD31 and Ulex europaeus agglutinin-1 (UEA-1) microvessels within the engineered grafts (HSS/EPCs) inosculated with recipient murine circulation. Limitation of murine CD31 immunoreactivity to HSS margins showed angiogenesis was attributable to human EPC at 2 weeks posttransplantation. Delivery of intravenous rhodamine-conjugated UEA-1 and microfil polymer to HSS/EPCs demonstrated enhanced perfusion by functional microvessels compared to HSS control without EPCs. CONCLUSION We successfully engineered functional microvessels in HSS by incorporating adult circulating EPCs. This autologous EC source can form vascular conduits enabling perfusion and survival of human bioengineered tissues. [source] Efficacy of the Flashlamp-Pumped Pulsed-Dye Laser in Nonsurgical Delay of Skin FlapsDERMATOLOGIC SURGERY, Issue 7 2003Ali Riza Erçöçen MD Objective. The purpose of this article was to determine the effectiveness of laser delay by use of the flashlamp-pumped pulsed-dye laser operating at a wavelength of 585 nm; to elucidate the comparable or dissimilar macroscopic, microscopic, and hemodynamic changes between laser and surgical delay methods; and to clarify the possible mechanisms underlying the delay effect of laser. Methods. A standardized caudally based random dorsal rat flap model was used in this study: Acute random skin flaps served as control subjects (group 1). Surgical delay was employed by incision of lateral longitudinal borders both without (group 2) and with (group 3) undermining, and laser delay methods were performed by laser irradiation of both lateral longitudinal borders (group 4) and the entire surface (group 5) of the proposed flap. Evaluation was done by histologic examination, India ink injection, laser Doppler perfusion imaging, and measurement of flap survival. Results. Histologically, dilation and hypertrophy of subpapillary and subdermal vessels were evident in groups 2, 3, and 4; on the other hand, degranulation of mast cells in the vicinity of occluded vessels at the 1st hour of laser delay and a striking mast cell proliferation and degranulation in association with newly formed vessels (angiogenesis) at the 14th day of laser delay were prominent in group 5. India ink injections revealed longitudinally arranged large-caliber vessels and cross-filling between the vessels of adjacent territories in groups, 2, 3, and 4, but only small-caliber vessels in group 5. Compared with the acute flaps, both surgical and laser delay significantly increased the mean flap perfusion to the maximal levels after a 14-day delay period, and all delay procedures improved flap survival; the most significant increase in surviving area was observed in group 3, whereas the less significant increase in surviving area was in group 5. Conclusion. This study demonstrates that laser delay is as effective as surgical delay and that laser delay by lasering lateral borders leads to dilation and longitudinal rearrangement of the existing vessels rather than angiogenesis, whereas laser delay by lasering the entire surface results in delay effect by inducing angiogenesis due to activation and degranulation of the mast cells. [source] Zebrafish notch signalling pathway mutants exhibit trunk vessel patterning anomalies that are secondary to somite misregulationDEVELOPMENTAL DYNAMICS, Issue 10 2010Christina Therapontos Abstract The Notch signalling pathway mutants, after-eight (aei), beamter (bea), and deadly-seven (des) have previously been used to study somitogenesis and neurogenesis. Notch signalling has also been shown to have roles in vascular development. However, vascular development in each of these three Notch mutants has not been described, and so their potential usefulness for further understanding the role of Notch signalling in angiogenesis is unknown. Here we demonstrate each of the mutants also exhibit vascular defects in inter-somitic vessel (ISV) positioning and patterning. Ectopic filopodia were also observed on the ISVs of the mutants. Ectopic filopodia are not due to loss of dll4. Somite expression of known vascular guidance cues, efnb2, sema3a2, and plexinD1 are disrupted, suggesting that the ISV vascular phenotype is due to disruption of these cues. Developmental Dynamics 239:2761,2768, 2010. © 2010 Wiley-Liss, Inc. [source] Developmental expression of Smoc1 and Smoc2 suggests potential roles in fetal gonad and reproductive tract differentiationDEVELOPMENTAL DYNAMICS, Issue 11 2009Dorothy E. Pazin Abstract SMOC1 and SMOC2 are matricellular proteins thought to influence growth factor signaling, migration, proliferation, and angiogenesis. We examined the expression and regulation of Smoc1 and Smoc2 in fetal gonad/mesonephros complexes to discover possible roles for these genes in gonad and mesonephros development. Smoc1 was upregulated at ,E10.75 in a center-to-poles wave in pre-Sertoli and pre-granulosa cells and its expression was greatly reduced in Wt1, Sf1, and Fog2 mutants. After E13.5, Smoc1 was downregulated in an anterior-to-posterior wave in granulosa cells but persisted in Sertoli cells, suggesting a sexually dimorphic requirement in supporting cell lineage differentiation. Smoc2 was expressed in Leydig cells, mesonephroi, and Wnt4 mutant ovaries, but not wildtype ovaries. Using organ culture, we determined that Smoc2 expression was dependent on Hedgehog signaling in testes, mesonephroi, and kidneys. Overall, these results demonstrate that SMOC1 and SMOC2 may mediate intercellular signaling and cell type,specific differentiation during gonad and reproductive tract development. Developmental Dynamics 238:2877,2890, 2009. © 2009 Wiley-Liss, Inc. [source] Analysis of the IKK,/NF-,B signaling pathway during embryonic angiogenesisDEVELOPMENTAL DYNAMICS, Issue 10 2008Yanjun Hou Abstract The nuclear factor-,B (NF-,B) signaling pathway regulates cellular growth, survival, differentiation and development. In this study, the functions of I,B kinase (IKK), in angiogenesis during mouse development were examined. Conditional disruption of the Ikk, locus in endothelial cells using the well-characterized Tie2-Cre transgene resulted in embryonic lethality between embryonic day (E) 13.5 and E15.5. Examination of the mutant embryos revealed that while deletion of Ikk, occurred in endothelial cells throughout the embryo, only the vascular network in the fetal liver was affected. Disruption of the fetal liver vasculature was accompanied by decreased cell proliferation and increased apoptosis of hepatocytes, but hematopoiesis was not affected. Increased apoptosis was not observed outside of fetal liver in the mutant embryos. These results indicate that the IKK,/NF-,B pathway plays a previously unappreciated role in development of the sinusoidal vasculature in the fetal liver and additionally that this pathway is critical in the crosstalk between endothelial cells and hepatocytes during mouse development. Developmental Dynamics 237:2926,2935, 2008. © 2008 Wiley-Liss, Inc. [source] SPARC is expressed by macroglia and microglia in the developing and mature nervous systemDEVELOPMENTAL DYNAMICS, Issue 5 2008Adele J. Vincent Abstract SPARC (secreted protein, acidic and rich in cysteine) is a matricellular protein that is highly expressed during development, tissue remodeling, and repair. SPARC produced by olfactory ensheathing cells (OECs) can promote axon sprouting in vitro and in vivo. Here, we show that in the developing nervous system of the mouse, SPARC is expressed by radial glia, blood vessels, and other pial-derived structures during embryogenesis and postnatal development. The rostral migratory stream contains SPARC that becomes progressively restricted to the SVZ in adulthood. In the adult CNS, SPARC is enriched in specialized radial glial derivatives (Müller and Bergmann glia), microglia, and brainstem astrocytes. The peripheral glia, Schwann cells, and OECs express SPARC throughout development and in maturity, although it appears to be down-regulated with maturation. These data suggest that SPARC may be expressed by glia in a spatiotemporal manner consistent with a role in cell migration, neurogenesis, synaptic plasticity, and angiogenesis. Developmental Dynamics 237:1449-1462, 2008. © 2008 Wiley-Liss, Inc. [source] HOXA13 directly regulates EphA6 and EphA7 expression in the genital tubercle vascular endotheliaDEVELOPMENTAL DYNAMICS, Issue 4 2007Carley A. Shaut Abstract Hypospadias, a common defect affecting the growth and closure of the external genitalia, is often accompanied by gross enlargements of the genital tubercle (GT) vasculature. Because Hoxa13 homozygous mutant mice also exhibit hypospadias and GT vessel expansion, we examined whether genes playing a role in angiogenesis exhibit reduced expression in the GT. From this analysis, reductions in EphA6 and EphA7 were detected. Characterization of EphA6 and EphA7 expression in the GT confirmed colocalization with HOXA13 in the GT vascular endothelia. Analysis of the EphA6 and EphA7 promoter regions revealed a series of highly conserved cis -regulatory elements bound by HOXA13 with high affinity. GT chromatin immunoprecipitation confirmed that HOXA13 binds these gene-regulatory elements in vivo. In vitro, HOXA13 activates gene expression through the EphA6 and EphA7 gene-regulatory elements. Together these findings indicate that HOXA13 directly regulates EphA6 and EphA7 in the developing GT and identifies the GT vascular endothelia as a novel site for HOXA13-dependent expression of EphA6 and EphA7. Developmental Dynamics 236:951,960, 2007. © 2007 Wiley-Liss, Inc. [source] Attenuation of retinal vascular development and neovascularization in transgenic mice over-expressing thrombospondin-1 in the lensDEVELOPMENTAL DYNAMICS, Issue 7 2006Zhifeng Wu Abstract Thrombospondin-1 (TSP1) is an endogenous inhibitor of angiogenesis and induces endothelial cell (EC) apoptosis. To study the role TSP1 plays during vascular development and neovascularization, we assessed the effects of ectopic TSP1 expression in the lens on retinal vascularization in transgenic mice. The TSP1 over-expressing mice showed abnormalities in the development of retinal vasculature. There was a dramatic decrease in the density of superficial and deep vascular plexuses of the retina in transgenic mice. The retinal vessels in TSP1 transgenic mice also appeared nonuniform and abnormal in maturation. We detected an increase in the number of EC undergoing apoptosis, which was compensated, in part, by an increase in cell proliferation in retinal vasculature of TSP1 transgenic mice. The TSP1 transgenic mice also exhibited increased levels of vessel obliteration and a limited preretinal neovascularization during oxygen-induced ischemic retinopathy (OIR). Our results indicate increased expression of TSP1 attenuates normal retinal vascularization and preretinal neovascularization during OIR. Therefore, modulation of TSP1 expression may provide an effective mechanism for regulation of ocular angiogenesis. Developmental Dynamics 235:1908,1920, 2006. © 2006 Wiley-Liss, Inc. [source] Vascular gene expression and phenotypic correlation during differentiation of human embryonic stem cellsDEVELOPMENTAL DYNAMICS, Issue 2 2005Sharon Gerecht-Nir Abstract The study of the cascade of events of induction and sequential gene activation that takes place during human embryonic development is hindered by the unavailability of postimplantation embryos at different stages of development. Spontaneous differentiation of human embryonic stem cells (hESCs) can occur by means of the formation of embryoid bodies (EBs), which resemble certain aspects of early embryos to some extent. Embryonic vascular formation, vasculogenesis, is a sequential process that involves complex regulatory cascades. In this study, changes of gene expression along the development of human EBs for 4 weeks were studied by large-scale gene screening. Two main clusters were identified,one of down-regulated genes such as POU5, NANOG, TDGF1/Cripto (TDGF, teratocarcinoma-derived growth factor-1), LIN28, CD24, TERF1 (telomeric repeat binding factor-1), LEFTB (left,right determination, factor B), and a second of up-regulated genes such as TWIST, WNT5A, WT1, AFP, ALB, NCAM1. Focusing on the vascular system development, genes known to be involved in vasculogenesis and angiogenesis were explored. Up-regulated genes include vasculogenic growth factors such as VEGFA, VEGFC, FIGF (VEGFD), ANG1, ANG2, TGF,3, and PDGFB, as well as the related receptors FLT1, FLT4, PDGFRB, TGF,R2, and TGF,R3, other markers such as CD34, VCAM1, PECAM1, VE-CAD, and transcription factors TAL1, GATA2, and GATA3. The reproducibility of the array data was verified independently and illustrated that many genes known to be involved in vascular development are activated during the differentiation of hESCs in culture. Hence, the analysis of the vascular system can be extended to other differentiation pathways, allocating human EBs as an in vitro model to study early human development. Developmental Dynamics 232:487,497, 2005. © 2004 Wiley-Liss, Inc. [source] Vascular regression is required for mesenchymal condensation and chondrogenesis in the developing limbDEVELOPMENTAL DYNAMICS, Issue 3 2001Melinda Yin Abstract Vascular regression occurs during limb mesenchymal cell condensation and chondrogenesis, but it is unclear whether it is required for these processes or is a secondary phenomenon without major regulatory roles. To address this issue, beads presoaked with the potent angiogenic factor vascular endothelial growth factor (VEGF) were implanted in the vicinity of the prospective digit 2 in early chick embryo wing buds and the effects on angiogenesis and digit development were determined over time. We found that VEGF treatment caused a marked local increase in blood vessel number and density. Strikingly, this was accompanied by inhibition of digit 2 development as revealed by lack of expression of chondrogenic transcription factor Sox9 and absence of Alcian blue staining. Vascular distribution and skeletal development in adjacent areas remained largely unaffected. Inhibition of digit formation and excess vascularization were both reversible upon further embryonic growth and dissipation of VEGF activity. When supernumerary digits were induced at the anterior limb margin by retinoic acid treatment, their development was also preceded by vascular regression; interestingly, cotreatment with VEGF inhibited supernumerary digit development as well. Direct exposure of limb mesenchymal cells in micromass cultures to VEGF caused no obvious effects on condensation and chondrogenesis, indicating that VEGF effects are not due to direct action on skeletal cells. Our results are the first to provide evidence that vascular regression is required for mesenchymal condensation and chondrogenesis. A model of how patterning mechanisms and vascular regression may intersect and orchestrate limb skeletogenesis is proposed. © 2001 Wiley-Liss, Inc. [source] NG2 proteoglycan is expressed exclusively by mural cells during vascular morphogenesisDEVELOPMENTAL DYNAMICS, Issue 2 2001Ugur Ozerdem Abstract Immunofluorescence mapping demonstrates that the NG2 proteoglycan is invariably expressed by the mural cell component of mouse neovascular structures. This pattern is independent of the developmental mechanism responsible for formation of the vasculature (vasculogenesis or angiogenesis). Thus, NG2 is expressed in the embryonic heart by cardiomyocytes, in developing macrovasculature by smooth muscle cells, and in nascent microvessels by vascular pericytes. Due to the scarcity of proven markers for developing pericytes, NG2 is especially useful for identification of this cell type. The utility of NG2 as a pericyte marker is illustrated by two observations. First, pericytes are associated with endothelial tubes at an early point in microvessel development. This early interaction between pericytes and endothelial cells has important implications for the role of pericytes in the development and stabilization of microvascular tubes. Second, the pericyte to endothelial cell ratio in developing capillaries varies from tissue to tissue. Because the extent of pericyte investment is likely to affect the physical properties of the vessel in question, it is important to understand the mechanisms that control this process. Additional insight into these and other aspects of vascular morphogenesis should be possible through use of NG2 as a mural cell marker. © 2001 Wiley-Liss, Inc. [source] Structural and biophysical simulation of angiogenesis and vascular remodeling ,DEVELOPMENTAL DYNAMICS, Issue 4 2001Ralf Gödde Abstract The purpose of this report is to introduce a new computer model for the simulation of microvascular growth and remodeling into arteries and veins that imitates angiogenesis and blood flow in real vascular plexuses. A C++ computer program was developed based on geometric and biophysical initial and boundary conditions. Geometry was defined on a two-dimensional isometric grid by using defined sources and drains and elementary bifurcations that were able to proliferate or to regress under the influence of random and deterministic processes. Biophysics was defined by pressure, flow, and velocity distributions in the network by using the nodal-admittance-matrix-method, and accounting for hemodynamic peculiarities like Fahraeus-Lindqvist effect and exchange with extravascular tissue. The proposed model is the first to simulate interdigitation between the terminal branches of arterial and venous trees. This was achieved by inclusion of vessel regression and anastomosis in the capillary plexus and by remodeling in dependence from hemodynamics. The choice of regulatory properties influences the resulting vascular patterns. The model predicts interdigitating arteriovenous patterning if shear stress-dependent but not pressure-dependent remodeling was applied. By approximating the variability of natural vascular patterns, we hope to better understand homogeneity of transport, spatial distribution of hemodynamic properties and biomass allocation to the vascular wall or blood during development, or during evolution of circulatory systems. © 2001 Wiley-Liss, Inc. [source] Telencephalic angiogenesis: a reviewDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 2001Floyd H Gilles MD No abstract is available for this article. [source] Protective role of pigment epithelium-derived factor (PEDF) in early phase of experimental diabetic retinopathyDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 7 2009Yumiko Yoshida Abstract Background Pigment epithelium-derived factor (PEDF) is the most potent inhibitor of angiogenesis in the mammalian eye, thus suggesting that PEDF may protect against proliferative diabetic retinopathy. However, a role for PEDF in early diabetic retinopathy remains to be elucidated. We investigated here whether and how PEDF could prevent the development of diabetic retinopathy. Methods Streptozotocin-induced diabetic rats were treated with or without intravenous injection of PEDF for 4 weeks. Early neuronal derangements were evaluated by electroretinogram (ERG) and immunofluorescent staining of glial fibrillary acidic protein (GFAP). Expression of PEDF and 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative stress, was localized by immunofluorescence. Vascular endothelial growth factor (VEGF) and p22phox expression were evaluated with western blots. Breakdown of blood retinal barrier (BRB) was quantified with fluorescein isothiocynate (FITC)-conjugated dextran. NADPH oxidase activity was measured with lucigenin luminescence. Results Retinal PEDF levels were reduced, and amplitudes of a- and b-wave in the ERG were decreased in diabetic rats, which were in parallel with GFAP overexpression in the Müller cells. Further, retinal 8-OHdG, p22phox and VEGF levels and NADPH oxidase activity were increased, and BRB was broken in diabetic rats. Administration of PEDF ameliorated all of the characteristic changes in early diabetic retinopathy. Conclusions Results suggest that PEDF could prevent neuronal derangements and vascular hyperpermeability in early diabetic retinopathy via inhibition of NADPH oxidase-driven oxidative stress generation. Substitution of PEDF may offer a promising strategy for halting the development of diabetic retinopathy. Copyright © 2009 John Wiley & Sons, Ltd. [source] Peripheral arterial disease in diabetes,a reviewDIABETIC MEDICINE, Issue 1 2010E. B. Jude Diabet. Med. 27, 4,14 (2010) Abstract Diabetic patients are at high risk for peripheral arterial disease (PAD) characterized by symptoms of intermittent claudication or critical limb ischaemia. Given the inconsistencies of clinical findings in the diagnosis of PAD in the diabetic patient, measurement of ankle-brachial pressure index (ABI) has emerged as the relatively simple, non-invasive and inexpensive diagnostic tool of choice. An ABI < 0.9 is not only diagnostic of PAD even in the asymptomatic patient, but is also an independent marker of increased morbidity and mortality from cardiovascular diseases. With better understanding of the process of atherosclerosis, avenues for treatment have increased. Modification of lifestyle and effective management of the established risk factors such as smoking, dyslipidaemia, hyperglycaemia and hypertension retard the progression of the disease and reduce cardiovascular events in these patients. Newer risk factors such as insulin resistance, hyperfibrinogenaemia, hyperhomocysteinaemia and low-grade inflammation have been identified, but the advantages of modifying them in patients with PAD are yet to be proven. Therapeutic angiogenesis, on the other hand, represents a promising therapeutic adjunct in the management of PAD in these patients. Outcomes after revascularization procedures, such as percutaneous transluminal angioplasty and surgical bypasses in diabetic patients, are poorer, with increased perioperative morbidity and mortality compared with that in non-diabetic patients. Amputation rates are higher due to the distal nature of the disease. Efforts towards increasing awareness and intensive treatment of the risk factors will help to reduce morbidity and mortality in diabetic patients with PAD. [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] HIF-1, protein expression is associated with the environmental inflammatory reaction in Barrett's metaplasiaDISEASES OF THE ESOPHAGUS, Issue 8 2009F. C. Ling SUMMARY The oxygen-regulated transcription factor subunit hypoxia inducible factor-1, (HIF-1,) is involved in angiogenesis, energy metabolism, cell survival, and inflammation. We examined the protein expression of HIF-1, within the progression of Barrett's sequence as well as the type and degree of the environmental inflammatory reaction. Squamous epithelium (SE), metaplastic, low- and high-grade dysplastic lesions, and tumor tissue of 57 resection specimens from patients with Barrett's adenocarcinoma were immunohistochemically analyzed. Active and chronic inflammatory reactions were classified according to the Updated Sydney System. HIF-1, protein expression increased significantly from SE to Barrett's metaplasia (BM) (P < 0.0001). From metaplasia through low- and high-grade dysplasia to cancer, no further increase could be detected. Active and chronic inflammation were also significantly different between SE and BM (P < 0.0001) but not during further progression in the sequence. HIF-1, protein expression did not correlate with histopathologic parameters or survival. HIF-1, protein expression pattern resembles the active and chronic environmental inflammatory reaction. All were significantly increased in metaplasia compared to SE without further change in tumor development. HIF-1, protein expression appears to be associated with inflammatory processes in the development of BM. [source] Association of mast cells with tumor angiogenesis in esophageal squamous cell carcinomaDISEASES OF THE ESOPHAGUS, Issue 2 2001M. Tomita The association of mast cells with tumor angiogenesis was investigated in patients with esophageal squamous cell carcinoma. Surgical specimens from 48 patients with esophageal squamous cell carcinoma were studied. Mast cells in tumor sections were stained with Alcian blue and safranin O. The number of mast cells was counted under light microscopy and the average count recorded. To highlight the microvessels, endothelial cells were stained with anti-human factor VIII antibody. Microvessel density was also counted. We found a significant correlation between mast cell count and microvessel density in patients with esophageal squamous cell carcinoma. Double staining of the microvessels revealed highly angiogenic areas densely populated with mast cells. There appears to be a direct correlation between the number of mast cells and tumor angiogenesis in patients with esophageal squamous cell carcinoma. [source] Vascular endothelial growth factor gene polymorphisms are associated with the risk of developing adenomyosisENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 5 2009Shan Kang Abstract Vascular endothelial growth factor (VEGF), a major mediator of angiogenesis and vascular permeability, may play a key role in the development of adenomyosis. The aim of this study was to investigate whether these four VEGF polymorphisms (,2578C/A, ,1154G/A, ,460C/T, and +936C/T) were associated with the risk of adenomyosis development. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in 174 adenomyosis patients and 199 frequency-matched control women. There were significant differences between patients and control group in allele frequencies and genotype distributions of the ,2578C/A polymorphisms (P = 0.010 and 0.044, respectively). Compared with the C/C genotype, the A/A + C/A genotype could significantly modify the risk of developing adenomyosis [odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.42,0.97]. For the ,1154G/A polymorphism, the allele frequencies and genotype distributions in patient group were significant different from those of the controls (P = 0.001 and 0.007, respectively). Compared with the G/G genotype, the A/A + G/A genotype could significantly decrease the risk of developing adenomyosis (OR = 0.51, 95% CI = 0.33,0.80). However, the genotype distributions and allele frequencies of the ,460C/T and +936C/T polymorphisms did not significantly differ between controls and patients (all P value > 0.05). The haplotype analysis suggested that the TGA (VEGF ,460/,1154/,2578) and CGA haplotypes exhibited a significant decrease in the risk of developing adenomyosis compared with the haplotype of TGC (OR = 0.64, 95% CI = 0.41,1.00; OR = 0.44, 95% CI = 0.21,0.93, respectively). The study indicated that the ,2578A or ,1154A allele of VEGF gene could significantly decrease the risk of adenomyosis and might be potentially protective factors for adenomyosis development. Environ. Mol. Mutagen., 2009. © 2009 Wiley-Liss, Inc. [source] Regional distribution of collagen and haemosiderin in the lungs of horses with exercise-induced pulmonary haemorrhageEQUINE VETERINARY JOURNAL, Issue 6 2009F. J. Derksen Summary Reasons for performing study: Regional veno-occlusive remodelling of pulmonary veins in EIPH-affected horses, suggests that pulmonary veins may be central to pathogenesis. The current study quantified site-specific changes in vein walls, collagen and haemosiderin accumulation, and pleural vascular profiles in the lungs of horses suffering EIPH. Hypothesis: In the caudodorsal lung regions of EIPH-affected horses, there is veno-occlusive remodelling with haemosiderosis, angiogenesis and fibrosis of the interstitium, interlobular septa and pleura. Methods: Morphometric methods were used to analyse the distribution and accumulation of pulmonary collagen and haemosiderin, and to count pleural vascular profiles in the lungs of 5 EIPH-affected and 2 control horses. Results: Vein wall thickness was greatest in the dorsocaudal lung and significantly correlated with haemosiderin accumulation. Increased venous, interstitial, pleural and septal collagen; lung haemosiderin; and pleural vascular profiles occurred together and changes were most pronounced in the dorsocaudal lung. Further, haemosiderin accumulation colocalised with decreased pulmonary vein lumen size. Vein wall thickening, haemosiderin accumulation and histological score were highly correlated and these changes occurred only in the caudodorsal part of the lung. Conclusion: The colocalisation of these changes suggests that regional (caudodorsal) venous remodelling plays an important role in the pathogenesis of EIPH. Potential relevance: The results support the hypothesis that repeated bouts of venous hypertension during strenuous exercise cause regional vein wall remodelling and collagen accumulation, venous occlusion and pulmonary capillary hypertension. Subjected to these high pressures, there is capillary stress failure, bleeding, haemosiderin accumulation and, subsequently, lung fibrosis. [source] Potential role of soluble angiopoietin-2 and Tie-2 in patients with inflammatory bowel diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2006I. E. Koutroubakis Abstract Background, Angiogenesis has been suggested to play an important role in inflammatory bowel disease (IBD). The aim of the study was to evaluate the serum markers of angiogenesis angiopoietin-2 (Ang-2) and soluble angiopoietin receptor Tie-2 in patients with ulcerative colitis (UC) and Crohn's disease (CD). Materials and methods, Serum Ang-2 and Tie-2 serum levels were measured in 160 IBD patients (79 UC and 81 CD) and in 80 matched healthy controls using commercially available enzyme-linked immunosorbent assays. Serum Ang-2 and Tie-2 levels were correlated with the disease activity, as well as the type, localization and treatment of the disease. Results, Median serum Ang-2 and Tie-2 levels were significantly higher in both the UC patients and the CD patients compared with the healthy controls (P < 0·05 and P < 0·001, respectively). The IBD patients with early disease (diagnosis < 2 years) had significantly higher (P = 0·04) median serum Ang-2 levels but significantly lower (P = 0·02) median serum Tie-2 levels as compared with IBD patients with late disease (diagnosis > 2 years). The CD patients with active disease had significantly higher levels of Ang-2 compared with non-active disease (P = 0·02). Serum levels of both Ang-2 and Tie-2 were not correlated with laboratory markers such as ESR, CRP, white blood cell count, platelet count and albumin. Conclusions, Serum Ang-2 and Tie-2 levels are elevated in patients with IBD. These markers may mediate angiogenesis and vascular permeability in the mucosa of patients with IBD. [source] Regulation of erythropoietin productionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2005K.-U. Eckardt Abstract The glycoprotein hormone erythropoietin (EPO) is an essential growth and survival factor for erythroid progenitor cells, and the rate of red blood cell production is normally determined by the serum EPO concentration. EPO production is inversely related to oxygen availability, so that an effective feedback loop is established, which controls erythropoiesis. Since recombinant EPO became available as an effective therapeutic agent, significant progress has also been made in understanding the basis of this feedback control. The main determinant of EPO synthesis is the transcriptional activity of its gene in liver and kidneys, which is related to local oxygen tensions. This control is achieved by hypoxia-inducible transcription factors (HIF), consisting of a constitutive ,-subunit and one of two alternative oxygen-regulated HIF, subunits (HIF-1, and HIF-2,). In the presence of oxygen (normoxia) the HIF, subunits are hydroxylated, which targets them for proteasomal degradation. Under hypoxia, because of the lack of molecular oxygen, HIF cannot be hydroxylated and is thereby stabilized. Although HIF-1, was the first transcription factor identified through its ability to bind to an enhancer sequence of the EPO gene, more recent evidence suggests that HIF-2, is responsible for the regulation of EPO. Although EPO is a prime example for an oxygen- regulated gene, the role of the HIF system goes far beyond the regulation of EPO, because it operates widely in almost all cells and controls a broad transcriptional response to hypoxia, including genes involved in cell metabolism, angiogenesis and vascular tone. Further evidence suggests that apart from its effect as an erythropoietic hormone EPO acts as a paracrine, tissue-protective protein in the brain and possibly also in other organs. [source] Paradox of simultaneous intestinal ischaemia and hyperaemia in inflammatory bowel diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2005O. A. Hatoum Abstract This review has focused on evidence regarding intestinal perfusion of inflammatory bowel disease (IBD). Basic investigation has defined an altered microvascular anatomy in the affected IBD bowel, which corresponds with diminished mucosal perfusion in the setting of chronic, long-standing inflammation. Diminished perfusion is linked to impaired wound healing, and may contribute to the continued refractory mucosal damage, which characterizes IBD. Alterations in vascular anatomy and physiology in IBD suggests additional possible mechanisms by which micro-vessels may contribute to the initiation and perpetuation of IBD. This begs the following questions: will angiogenesis within the gut lead to sustained inflammation, does the growing vasculature generate factors that transform the surrounding tissue and does angiogenesis generate vascular anastomosis within the gut, with shunting of blood away from the mucosal surface, impairment of metabolism and potentiation of gut damage? Further studies are required to define the mechanisms that underlie the vascular dysfunction and its role in pathophysiology of IBD. [source] | |||||||||||||||||||||||||||||||||||||||||||