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Angiogenic Phenotype (angiogenic + phenotype)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

The origin of the endothelial cells: an evo-devo approach for the invertebrate/vertebrate transition of the circulatory system

EVOLUTION AND DEVELOPMENT, Issue 4 2005
R. Muñoz-Chápuli
Summary Circulatory systems of vertebrate and invertebrate metazoans are very different. Large vessels of invertebrates are constituted of spaces and lacunae located between the basement membranes of endodermal and mesodermal epithelia, and they lack an endothelial lining. Myoepithelial differentation of the coelomic cells covering hemal spaces is a frequent event, and myoepithelial cells often form microvessels in some large invertebrates. There is no phylogenetic theory about the origin of the endothelial cells in vertebrates. We herein propose that endothelial cells originated from a type of specialized blood cells, called amoebocytes, that adhere to the vascular basement membrane. The transition between amoebocytes and endothelium involved the acquisition of an epithelial phenotype. We suggest that immunological cooperation was the earliest function of these protoendothelial cells. Furthermore, their ability to transiently recover the migratory, invasive phenotype of amoebocytes (i.e., the angiogenic phenotype) allowed for vascular growth from the original visceral areas to the well-developed somatic areas of vertebrates (especially the tail, head, and neural tube). We also hypothesize that pericytes and smooth muscle cells derived from myoepithelial cells detached from the coelomic lining. As the origin of blood cells in invertebrates is probably coelomic, our hypothesis relates the origin of all the elements of the circulatory system with the coelomic wall. We have collected from the literature a number of comparative and developmental data supporting our hypothesis, for example the localization of the vascular endothelial growth factor receptor-2 ortholog in hemocytes of Drosophila or the fact that circulating progenitors can differentiate into endothelial cells even in adult vertebrates. [source]

Hemostatic and hematological abnormalities in gain-of-function fps/fes transgenic mice are associated with the angiogenic phenotype

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2004
W. Sangrar
Summary. The Fps/Fes tyrosine kinase has been implicated in the regulation of hematopoiesis and inflammation. Mice expressing an activated variant of Fps/Fes (MFps) encoded by a gain-of-function mutant transgenic fps/fes allele (fpsMF) exhibited hematological phenotypes, which suggested that Fps/Fes can direct hematopoietic lineage output. These mice also displayed marked hypervascularity and multifocal-hemangiomas which implicated this kinase in the regulation of angiogenesis. Here we explored the potential involvement of Fps/Fes in the regulation of hemostasis through effects on blood cells and the vascular endothelium. Hematological parameters of fpsMF mice were characterized by peripheral blood analysis, histology, and transmission electron microscopy. Hemostasis parameters and platelet functions were assessed by flow cytometry and measurements of activated partial thromboplastin time, prothrombin time, thrombin clot time, platelet aggregation, bleeding times and in vitro fibrinolytic assays. Hematological and morphological analyses showed that fpsMF mice displayed mild thrombocytopenia, anemia, red cell abnormalities and numerous hemostatic defects, including hypofibrinogenemia, hyper-fibrinolysis, impaired whole blood aggregation and a mild bleeding diathesis. fpsMF mice displayed a complex array of hemostatic perturbations which are reminiscent of hemostatic disorders such as disseminated intravascular coagulation (DIC) and of hemangioma-associated pathologies such as Kasabach,Merritt phenomenon (KMS). These studies suggest that Fps/Fes influences both angiogenic and hemostatic function through regulatory effects on the endothelium. [source]

A Novel In Vitro Model of Canine Malignant Hemangioendothelioma

ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2005
D. Kühn
Introduction and Aim:, Canine malignant haemangioendothelioma is an aggressive neoplasia that affects mostly older dogs of large breeds with a strong predilection for the spleen, liver, heart and skin. The tumour originates in the vascular endothelium and consists of transformed cells forming large and leaky vessel-like structures. Prognosis is poor because surgery and chemotherapy have limited success in prolonging survival times and increasing quality of patients. A new strategy to treat this malignancy could be anti-angiogenic therapy based on the inhibition of proliferation, migration and three-dimensional organization of transformed cells. In order to reduce animal experiments, in vitro -models are required to test the safety and efficacy of anti-angiogenic drugs. So far only few models of angiogenesis are available using mostly human, rodent and bovine cells. Therefore, the aim of our study was to establish an in vitro model of canine haemangioendothelioma. Materials and Methods:, Tumours were collected from dogs during surgery or immediately after euthanasia. Isolation of cells was done from different areas of the tumours and by enzymatic digestion of the tissue. Cells were incubated in culture media with and without endothelial growth factors. Cells were characterized by lectin histochemistry using Dolichos biflorus agglutinin, Ulex europaeus agglutinin and Bandeiraea simplicifolia agglutinin I. Moreover, RT-PCR (polymerase chain reaction) was employed to investigate the expression of vascular endothelial growth factor (VEGF) and its endothelium-specific receptors VEGF-R1 and -R2. Results and Conclusions:, Different populations of cells were isolated and cultured successfully from canine malignant haemangioendothelioma. Cells show characteristics of microvascular endothelial cells of an angiogenic phenotype, i.e. the formation of spheroids and tube-like structures as well as strong labelling for Bandeiraea simplicifolia agglutinin I. Thus, morphological and glycohistochemical results confirm the vascular character of the cells isolated. RT-PCR showed expression of VEGF. However, endothelium-specific VEGF receptors were not expressed. Loss of typical receptors is common in cancer and may correlate with increased tumour dedifferentiation. [source]

Modulation of the angiogenic phenotype of normal and systemic sclerosis endothelial cells by gain,loss of function of pentraxin 3 and matrix metalloproteinase 12

ARTHRITIS & RHEUMATISM, Issue 8 2010
Francesca Margheri
Objective Studies have shown that in systemic sclerosis (SSc) endothelial cells, overproduction of matrix metalloproteinase 12 (MMP-12) and pentraxin 3 (PTX3) is associated with defective angiogenesis. This study was undertaken to examine whether overexpression of the relevant molecules could inhibit angiogenesis of normal microvascular endothelial cells (MVECs), and whether silencing of these molecules in SSc MVECs could restore the lost angiogenic properties of the cells in vitro and in vivo. Methods Transient transfection of MVECs with human MMP12 and PTX3 was performed by electroporation. Silencing of MMP12 and PTX3 was obtained by treatment with small interfering RNA, and treatment effects were validated by Western blotting with specific antibodies and a fluorimetric assay. In vitro cell migration and capillary morphogenesis were studied on Matrigel substrates. In vivo angiogenesis was studied using a Matrigel sponge assay in mice. Results Transfection of MMP12 and PTX3 in normal MVECs resulted in loss of proliferation, invasion, and capillary morphogenesis in vitro, attributed to truncation of the urokinase-type plasminogen activator receptor by MMP12 and to the anti,fibroblast growth factor 2/anti,vascular endothelial growth factor activity of PTX3. These effects were particularly evident in mixed populations of transfected normal MVECs (50% transfected with MMP12 and 50% with PTX3). Silencing of the same molecules in SSc MVECs increased their invasion in Matrigel. Single-gene silencing did not increase the capillary morphogenesis of SSc MVECs, whereas double-gene,silenced cells showed a burst of capillary tube formation. Culture medium of silenced SSc MVECs stimulated angiogenesis in assays of Matrigel sponge invasion in mice. Conclusion Overexpression of either MMP12 or PTX3 in normal MVECs blunts their angiogenic properties. Loss of function of MMP12 and PTX3 in SSc MVECs restores the ability of the cells to produce capillaries in vitro and induces vascularization in vivo on a Matrigel sponge. [source]