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At least 127 records · Page 7Linked to original sources
PubMed1999

Signaling via vascular endothelial growth factor receptors.

Angiogenesis, or development of blood vessels from preexisting vasculature, has important functions under both normal and pathophysiological conditions. Vascular endothelial growth factor receptors 1-3, also known as flt-1, KDR, and flt-4, are endothelial cell-specific receptor tyrosine kinases which serve as key mediators of the angiogenic responses. The review focuses on the signaling pathways that are initiated from these receptors and the recently identified VEGF coreceptor neuroplilin-1.

Endothelium, Vascular↗
PubMed2000

Angiogenic properties of the carcinoembryonic antigen-related cell adhesion molecule 1.

The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a member of the immunoglobulin superfamily, is expressed in microvessels of proliferating tissues such as endometrium, in tissues after wounding, and in solid human tumors. In microvascular human endothelial cells, purified native and recombinant CEACAM1 stimulates proliferation, chemotaxis, and tube formation. In the chorioallantoic membrane of the chicken, CEACAM1 induces angiogenesis. The angiogenic effects of CEACAM1 are additive to those of the vascular endothelial growth factor (VEGF). The expression of CEACAM1 is up-regulated by VEGF, and VEGF-induced in vitro tube formation is blocked completely by a monoclonal CEACAM1 antibody. These findings indicate that CEACAM1 is an angiogenic factor and an effector of VEGF.

Adenosine Triphosphatases↗
PubMed2002

Magic roundabout is a new member of the roundabout receptor family that is endothelial specific and expressed at sites of active angiogenesis.

We have used bioinformatic data mining to identify a novel, endothelial-specific gene encoding a protein with homology to the axon guidance protein roundabout (ROBO1). The new gene has been called magic roundabout (ROBO4; GenBank acc. no. AF361473) and is smaller than other members of the roundabout gene family. Thus, in the extracellular region, magic roundabout has only two of the five immunoglobulin and two of the three fibronectin domains present in other roundabout genes. Expression of magic roundabout in vitro was detected in only endothelial cells and was greater in cells exposed to hypoxia. In situ hybridization and immunohistochemistry validated the bioinformatic prediction that magic roundabout expression would be endothelial specific in vivo. Magic roundabout expression in the adult was restricted exclusively to sites of active angiogenesis, notably tumor vessels. The identification of magic roundabout shows that the roundabout gene family extends beyond neuronal tissue and that roundabout/slit interactions are likely to have a role in angiogenesis.

Amino Acid Sequence↗
PubMed2001

Therapeutic angiogenesis for ischemic cardiovascular disease.

In animal models of ischemia, a large body of evidence indicates that administration of angiogenic growth factors, either as recombinant protein or by gene transfer, can augment nutrient perfusion through neovascularization. While many cytokines have angiogenic activity, the best studied both in animal models and clinical trials are vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Clinical trials of therapeutic angiogenesis in patients with end-stage coronary artery disease have shown large increases in exercise time and marked reductions in symptoms of angina, as well as objective evidence of improved perfusion and left ventricular function. Larger scale placebo-controlled trials have been limited to intracoronary and intravenous administration of recombinant protein, and have not yet shown significant improvement in either exercise time or angina when compared to placebo. Larger scale placebo-controlled studies of gene transfer are in progress. Future clinical studies will be required to determine the optimal dose, formulation, route of administration and combinations of growth factors, as well as the requirement for endothelial progenitor cell or stem cell supplementation, to provide effective and safe therapeutic myocardial angiogenesis.

Animals↗
PubMed2000

Angiogenesis monitored by perfusion with a space-filling microbead suspension.

Numerous laboratories are focusing efforts on delivering gene products to induce or prevent the development of new blood vessels in adults, with the hope of rescuing ischemic tissues, circumventing cardiac bypass surgery, or inhibiting tumor growth. Current approaches to the assessment of vascular continuity involve the introduction of either dyes or fluorescent microspheres to track blood flow. However, dyes and dextrans are subject to leakage when vessels are hyperpermeable, a situation that may occur in studies of tumor vasculature and during efforts to stimulate therapeutic angiogenesis. Furthermore, the microspheres that are used for flow studies do not allow a comprehensive visual analysis of vascular continuity. Here we report a method for the visual assessment of microvascular continuity in mouse muscle under circumstances in which vessels are leaky. The approach involves perfusion of the vasculature with fluorescent beads that are much smaller than those used for flow studies. The suspension behaves like a fluid and completely fills the vessels, yet the beads do not leak from VEGF-permeablized capillaries and remain localized in histological sections. Use of beads with the proper fluorescence emission wavelengths allows immunofluorescent colocalization with vessel-specific markers. We compare this improved method with other methods for tracking vascular continuity involving dextrans and larger beads. This approach should aid in the dynamic study of tumor angiogenesis and the evaluation of efforts to deliver angiogenic factors.

Animals↗
PubMed1999

A comparison of two controlled-release delivery systems for the delivery of amiloride to control angiogenesis.

The diuretic amiloride has been reported to inhibit both Na+-H+ antiport and the urokinase-type plasminogen activator. As a consequence of these inhibitions, neovascularization may also be inhibited. We hypothesized that if amiloride could be effectively delivered in a site-specific manner, a system might be developed that could inhibit localized angiogenesis. In order to evaluate this possibility we conducted a study that compared two different controlled-release systems into which amiloride had been incorporated. The effectiveness of amiloride release from each delivery system was determined by quantitating angiogenic patterns in a chick chorioallantoic membrane (CAM) system using a fractal analysis software program. The two delivery systems compared were sucrose acetate isobutyrate (SAIB) and calcium alginate. Initial HPLC laboratory tests confirmed that amiloride could be released from both SAIB and calcium alginate in vitro in a sustained manner for 72 h. The CAM studies confirmed that neither SAIB nor calcium alginate alone promoted or inhibited angiogenesis when compared to nontreated controls. The release of amiloride from each delivery vehicle resulted in a significant (P < 0.05) inhibition of angiogenesis following both 24 and 48 h of release compared to controls. There was no difference in inhibition of angiogenesis, however, when comparing SAIB + amiloride treated CAMs with calcium alginate + amiloride treated CAMs. These data suggest that both SAIB and calcium alginate may be useful delivery vehicles for the localized application of amiloride to control angiogenesis. Such a system could potentially control tumor angiogenesis without systemic effects.

Alginates↗
PubMed2002

Identification of endothelial cell genes expressed in an in vitro model of angiogenesis: induction of ESM-1, (beta)ig-h3, and NrCAM.

Blood vessel growth by angiogenesis plays an essential role in embryonic development, wound healing, and tumor growth. To understand the molecular cues underlying this process we have used the PCR-based subtractive hybridization method, representational difference analysis, to identify genes upregulated in endothelial cells (EC) forming tubes in 3D collagen gels, compared to migrating and proliferating cells in 2D cultures. We identified several previously characterized angiogenic markers, including the alpha(v) chain of the alpha(v)beta3 integrin and plasminogen activator inhibitor-1, suggesting overlap in gene expression between tube-forming cells in vitro and in vivo. We also found a 2- to 10-fold upregulation of (beta)ig-h3 (a collagen-binding extracellular matrix protein), NrCAM (a "neural" cell adhesion molecule), Annexin II (a tPA receptor), ESM-1 (an EC-specific molecule of unknown function), and Id2 (an inhibitory bHLH transcription factor). We identified a novel splice variant of the ESM-1 gene and also detected dramatically enhanced expression of ESM-1 and (beta)ig-h3 in several tumors. Antisense oligonucleotides to (beta)ig-h3 blocked both gene expression and tube formation in vitro, suggesting that (beta)ig-h3 may play a critical role in EC-matrix interactions. These data expand the suite of genes implicated in vascular remodeling and angiogenesis.

Alternative Splicing↗
PubMed2002

Vascular and neuronal effects of VEGF in the nervous system: implications for neurological disorders.

Vascular endothelial growth factor (VEGF) was originally discovered as an endothelial-specific growth factor. While the predominant role of this growth factor in the formation of new blood vessels (angiogenesis) is unquestioned, recent observations indicate that VEGF also has direct effects on neurons and glial cells, and stimulates their growth, survival and axonal outgrowth. Because of these pleiotropic effects, VEGF has now been implicated in several neurological disorders both in the preterm infant (leukomalacia) and the adult (stroke, neurodegeneration, cerebral and spinal trauma, ischemic and diabetic neuropathy, nerve regeneration). A challenge for the future is to unravel to what extent the effect of VEGF in these disorders relates to its angiogenic activity or direct neurotrophic effect.

Animals↗
PubMed2006

Principles and therapeutic implications of angiogenesis, vasculogenesis and arteriogenesis.

The vasculature is the first organ to arise during development. Blood vessels run through virtually every organ in the body (except the avascular cornea and the cartilage), assuring metabolic homeostasis by supplying oxygen and nutrients and removing waste products. Not surprisingly therefore, vessels are critical for organ growth in the embryo and for repair of wounded tissue in the adult. Notably, however, an imbalance in angiogenesis (the growth of blood vessels) contributes to the pathogenesis of numerous malignant, inflammatory, ischaemic, infectious and immune disorders. During the last two decades, an explosive interest in angiogenesis research has generated the necessary insights to develop the first clinically approved anti-angiogenic agents for cancer and blindness. This novel treatment is likely to change the face of medicine in the next decade, as over 500 million people worldwide are estimated to benefit from pro- or anti-angiogenesis treatment. In this following chapter, we discuss general key angiogenic mechanisms in health and disease, and highlight recent developments and perspectives of anti-angiogenic therapeutic strategies.

Angiogenesis Inhibitors↗