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Results for “Neovascularization, Pathologic”

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At least 847 records · Page 47Linked to original sources
PubMed2005

Persistent vascular defects in lung allografts attributed to defective endogenous endothelial progenitors.

BACKGROUND: A major pathological finding in human newborns with pulmonary hypoplasia and congenital diaphragmatic hernia is the presence of vascular abnormalities in lungs. Vasculogenesis/angiogenesis are crucial to lung development. To study lung alveolar development, including microvascular formation in fetal lung implants, Schwarz et al. [1] developed a subcutaneous allograft model. We adopted their model to assess the influence of neovascularization or the "host-graft vascular development" on hypoplastic lung structure and growth. MATERIALS AND METHODS: Normal and hypoplastic lungs at pseudoglandular stage were implanted subcutaneously under the dorsolateral fold of immunocompromised nude mice (athymic, nu/nu). Lung allografts were removed and assessed at 2, 4, 6, and 8 weeks postimplantation. RESULTS: Neovascularization of implanted lungs from subcutaneous vasculature of nude mice resulted in varying degrees of maturation of implanted normal and hypoplastic lungs. By 4 weeks, implanted normal lungs contained Type 2-like cells and by 7 to 8 weeks, Type 2 and Type 1-like cells, air spaces had enlarged, and surfactant secretion was observed. Despite some differentiation and maturation of hypoplastic lungs, there was more mesenchymal tissue, no secondary septa, and smaller air spaces compared to normal lungs. CONCLUSIONS: (a) Neovascularization or host-graft vascular development occurs in both normal and hypoplastic lung allografts. (b) Development and maturation of implanted normal and hypoplastic lungs follow the establishment of the vascular connections between the host and grafts. (c) The host-graft vascular connections do not improve the growth of normal or hypoplastic lungs. (d) Neovascularization failed to overcome the embryonic defects in vascular formation and the pulmonary vasculogenesis remained defective in hypoplastic lung allografts, which may be attributed to the defective endogenous endothelial progenitor cells.

Animals↗
PubMed2001

Up-regulation of vascular endothelial growth factor in breast cancer cells by the heregulin-beta1-activated p38 signaling pathway enhances endothelial cell migration.

Heregulin (HRG) belongs to a family of polypeptide growth factors that bind to receptor tyrosine kinases ErbB3 and ErbB4. HRG binding induces ErbB3 and ErbB4 heterodimerization with ErbB2, activating downstream signal transduction. Vascular endothelial growth factor (VEGF) is a primary regulator of physiological angiogenesis and is a major mediator of pathological angiogenesis, such as tumor-associated neovascularization. In this study, we demonstrate that HRG-beta1 increased secretion of VEGF from breast cancer cells in a time- and dosage-dependent manner and that this increase resulted from up-regulation of VEGF mRNA expression via transcriptional activation of the VEGF promoter. Deletion and mutational analysis revealed that a CA-rich upstream HRG response element located between nucleotide-2249 and -2242 in the VEGF promoter mediated HRG-induced transcriptional up-regulation of VEGF. While investigating the downstream signaling pathways involved in HRG-mediated up-regulation of VEGF, we found that HRG activated extracellular signal-regulated protein kinases, Akt kinase, and p38 mitogen-activated protein kinase (MAPK). However, only the specific inhibitor of p38 MAPK (SB203580), not extracellular signal-regulated kinase inhibitor PD98059 nor the inhibitor of phosphatidylinositol 3-kinase-Akt pathway (Wortmannin), blocked the up-regulation of VEGF by HRG. The HRG-stimulated secretion of VEGF from breast cancer cells resulted in increased migration of murine lung endothelial cells, an activity that was inhibited by either VEGF-neutralizing antibody or SB203580. These results show that HRG can activate p38 MAPK to enhance VEGF transcription via an upstream HRG response element, leading to increased VEGF secretion and angiogenic response in breast cancer cells.

Breast Neoplasms↗
PubMed2002

Endothelial cell heterogeneity and organ specificity.

Endothelial cells consist of a heterogeneous population covering the entire inner surface of blood vessels. This review will focus on the factors influencing this heterogeneity including: (1) morphological and functional differences between large and small vessels and between cells derived from various microvascular endothelial beds; (2) the microenvironment and extracellular matrix modulating the phenotype; (3) different response to growth factors; (4) organ specificity reflecting the cumulative expression of post-translation modifications and also the expression of unique genes under the control of organ-specific regulatory elements; and (5) pathological conditions, such as tumor growth, which is accompanied by the development of a characteristic tumor vasculature and tumors formed by endothelial cells.

Animals↗
PubMed1999

[Angiogenesis--vascular endothelial growth factor and its receptors].

Angiogenesis is a crucial biological process not only in the formation of cardiovascular system and organization of tissues in embryo but also in a variety of diseases including solid tumor growth and diabetic retinopathy. Several protein factors crucial for regulation of angiogenesis have recently been identified. Among these factors, VEGF is considered to be the most important regulator for vascular endothelial cell growth and differentiation both in physiological and pathological conditions. Relationship between VEGF and other regulatory factors such as Angiopoietins should be elucidated to further understand the dynamic process of angiogenesis.

Animals↗
PubMed2005

Pododermal angiogenesis and angioadaptation in the bovine claw.

Pododermal microvascularization has been suggested to play a key role in the physiological function of the bovine claw and in the pathogenesis of claw diseases. According to our working hypothesis, angiogenesis plays a central role in the physiological and pathological function of the claw and is induced by the pro-angiogenic vascular endothelial growth factor (VEGF). As a basis for further research, the aim of the present study was to examine the mechanisms of pododermal angiogenesis in the functional adaptation of the microvasculature of the claw in histological serial sections and microcorrosion casts of healthy juvenile and adult claws as well as pathologically altered claws. Scanning electron microscopy of microcorrosion casts allowed assessment of the 3D aspect of pododermal angiogenesis and angioadaptation, and was substantiated by a concomitant examination of a 3D in vitro model of angiogenesis based on cultured bovine microvascular endothelial cells. Particularly in the juvenile, but also in the adult claw, sprouting and intussusceptive angioadaptation was demonstrated and resembled the respective stages of in vitro angiogenesis. Evidence of angiogenic processes was also detected in the pathologically altered claws displaying symptoms of subclinical laminitis and/or the digital dermatitis complex. The detected angioadaptation was visible expression of the increased metabolic demands of the claw caused by the growing body weight load. Angiogenic remodeling of the pododermal angioarchitecture was also the connectional reparative principle in pathologically altered claws. Related research perspectives for prophylaxis and therapy of claw diseases are discussed.

Adaptation, Physiological↗
PubMed2003

Molecular regulation of vessel maturation.

The maturation of nascent vasculature, formed by vasculogenesis or angiogenesis, requires recruitment of mural cells, generation of an extracellular matrix and specialization of the vessel wall for structural support and regulation of vessel function. In addition, the vascular network must be organized so that all the parenchymal cells receive adequate nutrients. All of these processes are orchestrated by physical forces as well as by a constellation of ligands and receptors whose spatio-temporal patterns of expression and concentration are tightly regulated. Inappropriate levels of these physical forces or molecules produce an abnormal vasculature--a hallmark of various pathologies. Normalization of the abnormal vasculature can facilitate drug delivery to tumors and formation of a mature vasculature can help realize the promise of therapeutic angiogenesis and tissue engineering.

Animals↗
PubMed1998

[Angiotensin and its mediators. Their pathogenic and clinical significance in "angiogenic diseases"].

Angiogenesis, the production of new blood vessels, plays an important role in a number of physiological and pathological processes, such as development, tissue repair, atherosclerosis, ischemic heart diseases, inflammation and tumor progression. A number of mediators including cytokines, heparin-dependent and -independent growth factors, proteolytic enzymes, extracellular matrix components, cellular adhesion molecules and others, have been implicated in angiogenesis. Certain angiostatic cytokines, growth factor antagonists, steroids, protease inhibitors, antibiotics, antirheumatic drugs, tissue-derived inhibitors and others inhibit neovascularization. Angiogenesis research has important clinical relevance, as targeting angiogenic and angiostatic processes by using angiogenesis inhibitors, receptor antagonists, antibodies, enzyme inhibitors, tumor suppressor genes and other forms of gene therapy, may be a potential therapeutic tool in "angiogenic diseases".

Angiogenesis Inducing Agents↗
PubMedDate not supplied

Interaction of angiogenic and immune mechanisms in the eye.

Although a critical physiologic process, angiogenesis also contributes to the pathology associated with a variety of ocular diseases. Here we describe immune factors that regulate angiogenesis and review recent attempts to exploit these factors in animal models of ocular disease.

Animals↗
PubMed1999

Angiogenesis and arthritis.

Indices of angiogenesis are increased in synovia from patients with arthritis, and vascular proliferation may contribute to the pathogenesis of synovitis, pannus growth, bone and cartilage destruction, and osteophyte formation. Pharmacological inhibition of angiogenesis therefore has potential as a therapeutic strategy in human arthritis. However, vascular growth is also essential for normal development, female reproduction and tissue repair. Selective inhibition of undesirable angiogenesis requires an understanding of the different regulatory mechanisms in pathological and physiological angiogenesis. This review outlines the evidence that the rate of angiogenesis is increased in the inflamed human synovium, and possible approaches to, and consequences of, the modulation of vascular growth.

Arthritis↗
PubMed2006

[The role of matrix metalloproteinases and their tissue inhibitors in angiogenesis].

Cellular aspect of angiogenesis - the multilevel process involving the growth of new blood vessels from pre-existing vessels--includes migration and proliferation of the cells as well as remodelling of their environment--extracellular matrix (ECM). The key role in ECM remodelling is played by proteolytic enzymes classified as matrix metalloproteinases (MMPs). Recent research shows that performed by MMPs degradation of vascular ECM components is a significant event ocurring during angiogenesis. This process enables migration of endothelial cells that is crucial part in new vessel formation. MMPs also release sequestered angiogenic molecules, such as VEGF, bFGF and TGF-beta. Angiogenesis is a normal process in growth and development, as well as in wound healing, monthly reproductive cycle and during pregnancy. However, this is also a fundamental step in such conditions as malignancies, inflammation or ischaemia. The influence of MMPs on agiogenesis as terminal agents in many physio- and pathological events makes this group of enzymes very promissing aim of new therapeutic strategies based on modulation of angiogenesis.

Animals↗
PubMed2003

Angiogenesis assays: a critical overview.

BACKGROUND: Angiogenesis, the formation of new blood vessels, is an integral part of both normal developmental processes and numerous pathologies, ranging from tumor growth and metastasis to inflammation and ocular disease. Angiogenesis assays are used to test efficacy of both pro- and antiangiogenic agents. METHODS: Most studies of angiogenesis inducers and inhibitors rely on various models, both in vitro and in vivo, as indicators of efficacy. In this report we describe the principal methods now in use: the in vivo Matrigel plug and corneal neovascularization assays, the in vivo/in vitro chick chorioallantoic membrane (CAM) assay, and the in vitro cellular (proliferation, migration, tube formation) and organotypic (aortic ring) assays. We include description of two new methods, the chick aortic arch and the Matrigel sponge assays. CONCLUSIONS: In vitro tests are valuable, can be carried out expeditiously, and lend themselves to quantification, but must be interpreted with extreme caution. In vitro tests are best viewed as providing initial information, subject to confirmation by in vivo assays. Multiple tests should be used to obtain maximum benefit from in vitro tests. In vivo tests are more difficult and time-consuming to perform, thereby limiting the number of tests that can run at any one time. Quantification is generally more difficult as well. However, in vivo assays are essential because of the complex nature of vascular responses to test reagents, responses that no in vitro model can fully achieve.

Animals↗
PubMed2006

PPAR gamma represses VEGF expression in human endometrial cells: implications for uterine angiogenesis.

UNLABELLED: Endometrial vasculature supports physiological uterine growth, embryonic implantation and endometrial pathology. Vascular endothelial growth factor (VEGF) is regulated by diverse developmental and hormonal signals, including eicosanoid ligands of PPARgamma. The action of natural and synthetic PPARgamma ligands on VEGF expression in primary and transformed human endometrial cell cultures was established by quantifying endogenous gene expression and transfected VEGF gene reporters. VEGF promoter-luciferase constructs were truncated and mutated to map functional sequences. Endometrial tissues and cells express PPARgamma protein. Treatment of transformed and primary endometrial cells with rosiglitazone, a synthetic PPARgamma agonist, or prostaglandin 15-deoxy-Delta12-14 J(2), a naturally occurring eicosanoid ligand, decreased VEGF protein secretion. In transiently transfected Ishikawa cells, rosiglitazone repressed VEGF gene promoter-luciferase activation with an IC(50) approximately approximately 50 nM. Truncated and mutated VEGF promoter constructs revealed that the PPARgamma-regulated domain is a direct repeat (DR)-1 motif -443 bp upstream of the transcriptional start site. CONCLUSIONS: PPARgamma ligands repress VEGF gene expression via a PPARgamma-responsive element (PPRE) in the VEGF gene promoter. Agonists of this nuclear receptor might be exploited pharmacologically to inhibit pathological vascularization in complications of pregnancy, endometriosis and endometrial adenocarcinoma.

Cell Line, Tumor↗
PubMedDate not supplied

Angiogenesis: basic and clinical aspects.

The cardiovascular system is the first functional organ system to develop in the vertebrate embryo. A widely accepted view is that blood vessels arise through two mechanisms during development, vasculogenesis and angiogenesis. New vessels in the adult arise mainly through angiogenesis, although vasculogenesis also may occur. The existence of a postnatal vasculogenesis is also supported by the evidence that both endothelial cells and endothelial precursor cells co-exist in the circulation. Angiogenesis is a biological process by which new capillaries are formed and it occurs in many physiological and pathological conditions. It is controlled by the net balance between molecules that have positive and negative regulatory activity and this concept had led to the notion of the "angiogenic switch", depending on an increased production of one or more of the positive regulators of angiogenesis. Considerable benefit can be derived in the clinical setting from manipulating angiogenesis, either positively or negatively. There is a variety of important clinical situations in which it would be desiderable to promote angiogenic processes, such as situations in which it would be desiderable to promote angiogenic processes, such as for the induction of collateral vascularization in an ischemic heart or limb. Conversely, there are pathologic conditions in which preventing angiogenic processes could be useful in the treatment of a growing tumor or a chronic inflammatory process.

Angiogenesis Inhibitors↗
PubMed1996

Cooperative effect of TNFalpha, bFGF, and VEGF on the formation of tubular structures of human microvascular endothelial cells in a fibrin matrix. Role of urokinase activity.

In angiogenesis associated with tissue repair and disease, fibrin and inflammatory mediators are often involved. We have used three-dimensional fibrin matrices to investigate the humoral requirements of human microvascular endothelial cells (hMVEC) to form capillary-like tubular structures. bFGF and VEGF165 were unable to induce tubular structures by themselves. Simultaneous addition of one or both of these factors with TNFalpha induced outgrowth of tubules, the effect being the strongest when bFGF, VEGF165, and TNFalpha were added simultaneously. Exogenously added u-PA, but not its nonproteolytic amino-terminal fragment, could replace TNFalpha, suggesting that TNFalpha-induced u-PA synthesis was involved. Soluble u-PA receptor (u-PAR) or antibodies that inhibited u-PA activity prevented the formation of tubular structures by 59-99%. epsilon-ACA and trasylol which inhibit the formation and activity of plasmin reduced the extent of tube formation by 71-95%. TNFalpha or u-PA did not induce tubular structures without additional growth factors. bFGF and VEGF165 enhanced of the u-PAR by 72 and 46%, but TNFalpha itself also increased u-PAR in hMVEC by 30%. Induction of mitogenesis was not the major contribution of bFGF and VEGF165 because the cell number did not change significantly in the presence of TNFalpha, and tyrphostin A47, which inhibited mitosis completely, reduced the formation of tubular structures only by 28-36%. These data show that induction of cell-bound u-PA activity by the cytokine TNFalpha is required in addition to the angiogenic factors VEGF165 and/or bFGF to induce in vitro formation of capillary-like structures by hMVEC in fibrin matrices. These data may provide insight in the mechanism of angiogenesis as occurs in pathological conditions.

Capillaries↗
PubMed2004

Vascular endothelial growth factor and angiogenesis.

Angiogenesis is a hallmark of wound healing, the menstrual cycle, cancer, and various ischemic and inflammatory diseases. A rich variety of pro- and antiangiogenic molecules have already been discovered. Vascular endothelial growth factor (VEGF) is an interesting inducer of angiogenesis and lymphangiogenesis, because it is a highly specific mitogen for endothelial cells. Signal transduction involves binding to tyrosine kinase receptors and results in endothelial cell proliferation, migration, and new vessel formation. In this article, the role of VEGF in physiological and pathological processes is reviewed. We also discuss how modulation of VEGF expression creates new therapeutic possibilities and describe recent developments in this field.

Angiogenesis Modulating Agents↗
PubMed2006

Angiogenesis--a new target for future therapy.

Development of blood vessels from in situ differentiating endothelial cells (EC) is called vasculogenesis, whereas sprouting of new blood vessels from the pre-existing ones is termed angiogenesis or neovascularisation. Angiogenesis, the growth of new blood vessels, is essential during tissue repair, foetal development, and female reproductive cycle. In contrast, uncontrolled angiogenesis promotes tumor and retinopathies, while inadequate angiogenesis can lead to coronary artery disease. A balance between pro-angiogenic and anti-angiogenic growth factors and cytokines tightly controls angiogenesis. With the identification of several proangiogenic molecules such as the vascular endothelial cell growth factor (VEGF), the fibroblast growth factors (FGFs), and the angiopoietins, and the recent description of specific inhibitors of angiogenesis such as platelet factor-4, angiostatin, endostatin, and vasostatin, it is recognized that therapeutic interference with vasculature formation offers a tool for clinical applications in various pathologies. Inhibition of angiogenesis can prevent diseases such as cancer, diabetic nephropathy, arthritis, psoriasis, whereas stimulation of angiogenesis is beneficial in the treatment of coronary artery disease (CAD), cardiac failure, tissue injury, etc. One of the most specific and critical regulators of angiogenesis is vascular endothelial growth factor (VEGF), which regulates endothelial proliferation, permeability, and survival. Substantial evidence also implicates VEGF as an angiogenic mediator in tumors and intraocular neovascular syndromes, and numerous clinical trials are presently testing the hypothesis that inhibition of VEGF may have therapeutic value.

Adiponectin↗
PubMed2002

Biomedical significance of endothelial cell specific growth factor, angiopoietin.

Until recently, vascular endothelial growth factor (VEGF) was the only growth factor proven to be specific and critical for blood vessel formation. Other long-known factors, such as the fibroblast growth factors (FGFs), platelet-derived growth factor, or transforming growth factor-beta, had profound effects in endothelial cells. But such factors were nonspecific, in that they could act on many other cells, and it seemed unlikely that these growth factors would be effective targets for treatment of endothelial cell diseases. A recently discovered endothelial cell specific growth factor, angiopoietin, has greatly contributed to our understanding of the development, physiology, and pathology of endothelial cells (Davis et al., 1996; Yancopoulos et al., 2000). The recent studies that identified and characterized the physiological and pathological roles of angiopoietin have allowed us to widen and deepen our knowledge about blood vessel formation and vascular endothelial function. Therefore, in this review, we describe the biomedical significance of these endothelial cell growth factors, the angiopoietins, in the vascular system under normal and pathological states.

Alternative Splicing↗