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Vascular Formation (vascular + formation)
Selected AbstractsVascular endothelial growth factor in edematous mouse embryos induced by retinoic acid in uteroCONGENITAL ANOMALIES, Issue 2 2001Yoshiko Yasuda ABSTRACT, Vascular endothelial growth factor (VEGF) is induced by hypoxic environment and contributes to vascular formation in both developing embryos and adults. Exogenous retinoic acid (RA) induces avascular yolk sacs with anemic stunted embryos of day 9 and 10 of gestation when RA is given to pregnant mice on day 6, 6.5 or 7 of pregnancy (Yasuda et al., 1996). We undertook the present studies to find out whether VEGF is activated and plays any role in those RA-exposed embryos. Embryos were obtained from dams given 60 mg/kg of RA on day 6 or 7 of pregnancy and sacrificed three days later. Most RA-exposed embryos showed edematous swelling without prominent vascular nets, but had beating heart tubes on day 9 and day 10 of gestation. Microscopic examination of developing tissue components showed various degrees of degeneration, and distension of the dorsal aorta when the body cavity was dosed. Northern blot analysis revealed expression of VEGF mRNA in the RA-exposed and control embryos. The highest expression of VEGF mRNA was seen in the embryos of day 10 exposed to RA on day 7, and these embryos had a significantly lower ATP content than did the controls (p < 0.01). Immunoreactive VEGF was detectable in both experimental and control embryos; in the former it was especially visible in the distended neuroepithelium, endothelium and membranes. These VEGF-immunoreactive regions also expressed another permeability factor, bradykinin. These findings suggest that VEGF upregulated by hypoxic conditions in edematous embryos induced by RA exposure in utero acts as hyperpermeability. [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] Glioblastoma cells incorporate into tumor vasculature and contribute to vascular radioresistanceINTERNATIONAL JOURNAL OF CANCER, Issue 9 2010Candice A. Shaifer Abstract Glioblastoma multiforme (GBM) remains the most devastating neoplasm of the central nervous system and has a dismal prognosis. Ionizing radiation represents an effective therapy for GBM, but radiotherapy remains only palliative because of radioresistance. In this study, we demonstrate that glioma cells participate in tumor vascularization and contribute to vascular radioresistance. Using a 3-dimensional coculture system, we observed an intimate interaction of glioma cells with endothelial cells whereby endothelial cells form vascular structures, followed by the recruitment and vascular patterning of glioma cells. In addition, tumor cells stabilize the vascular structures and render them radioresistant. Blocking initial endothelial vascular formation with endothelial-specific inhibitors prevented tumor cells from forming any structures. However, these inhibitors exhibited minimum effects on vascular structures formed by tumor cells, due to the absence of the targeted receptors on tumor cells. Consistent with the in vitro findings, we show that glioma cells form perfused blood vessels in xenograft tumor models. Together, these data suggest that glioma cells mimic endothelial cells and incorporate into tumor vasculature, which may contribute to radioresistance observed in GBM. Therefore, interventions aimed at the glioma vasculature should take into consideration the chimeric nature of the tumor vasculature. [source] Genetic and epigenetic mechanisms in the early development of the vascular systemJOURNAL OF ANATOMY, Issue 2 2006Domenico Ribatti Abstract The cardiovascular system plays a critical role in vertebrate development and homeostasis. Vascular development is a highly organized sequence of events that requires the correct spatial and temporal expression of specific sets of genes leading to the development of a primary vascular network. There have been intensive efforts to determine the molecular mechanisms regulating vascular growth and development, and much of the rationale for this has stemmed from the increasing clinical importance and therapeutic potential of modulating vascular formation during various disease states. [source] Development of the coronary vasculature and its implications for coronary abnormalities in general and specifically in pulmonary atresia without ventricular septal defectACTA PAEDIATRICA, Issue 2004AC Gittenberger-de Groot Aim: Coronary vascular anomalies are an important factor in congenital heart disease in the neonate. However, our knowledge of the pathomorphogenesis is still defective. Material and methods: 1) Study of coronary anomaly variations in congenital heart disease using specimens and 2) study of the role of epicardium-derived cells (EPDC) and neural crest cells in coronary vascular formation using quail-chicken chimeras. Results: The clinical and pathological data revealed the existence of ventriculo-coronary arterial communications during fetal life before pulmonary atresia was established. This supported a primary coronary developmental anomaly as the origin of some cases of pulmonary atresia as opposed to other cases in which the pulmonary orifice atresia was the primary anomaly. Our experimental work showed the high relevance of the development of the epicardium and epicardium-derived cells for the formation of the coronary vasculature, and showed the coronary vascular ingrowth into the myocardium and subsequently into the aorta and the right atrium. The absence of epicardium-derived cells leads to embryonic death, while delayed outgrowth could result in the absence of the main coronary arteries to pinpoint orifice formation. In these cases, the circulation was maintained through ventriculocoronary arterial communications. Neural crest cells were important for the patterning of the coronary vasculature. We have extended this knowledge to a number of other heart malformations. Conclusions: Coronary vascular anomalies are highly linked to the development of extracardiac contributors like the epicardium and the neural crest. A proper interaction between these cell types and the myocardium and aortic arterial wall are important for normal vascular development. [source] Histological Assessment of Selected Blood Vessels of the Phocid Seals (Northern Elephant and Harbour Seals)ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 3 2010H. Smodlaka Summary Phocid seals exhibit vascular adaptations that allow them to undertake prolonged deep dives. These vascular adaptations are either unique to phocids, or are modified vascular equivalents to those present in terrestrial mammals. One such adaptation, the aortic bulb, is a spherical enlargement of the ascending aorta specific to phocid seals. Its histological make-up consists of a reinforced tunica media with circular and longitudinal layers of elastic fibres. This reinforcement enables multi-axial deformation of the aortic bulb, thus complementing its function as a prominent elastic reservoir or ,windkessel'. A second adaptation, the hepatic sinus, is an asymmetrical dilation of the abdominal portion of the caudal vena cava and accompanying hepatic veins. The hepatic sinus is comprised of a relatively thin tunica media, with a scant smooth muscle component. The bulk of the sinus wall is comprised of tunica adventitia. A third vascular adaptation distinctive to the phocids is the pericardial venous plexus, composed of convoluted veins circumnavigating the perimeter of the heart. Microscopically, these veins have a thick tunica media and also contain valves. Smaller arteries, venules and distinct capillary beds are observed interspersed in-between these veins. It can be hypothesized, that in seals, certain vascular embryonic development may be arrested at an earlier embryonic stage, resulting in these unusual vascular formations. These modifications play a vital role in blood pressure regulation and distribution of oxygenated blood during prolonged deep diving. The purpose of this work was to elucidate the histological aspects of these unique vascular modifications and relate them to specific function. [source] Vascular Patterns in Glioblastoma Influence Clinical Outcome and Associate with Variable Expression of Angiogenic Proteins: Evidence for Distinct Angiogenic SubtypesBRAIN PATHOLOGY, Issue 2 2003Peter Birner MD No data exist on angiogenic patterns and their prognostic impact in human glioblastoma. Such data are relevant for translation of antiangiogenic therapies into clinical applications. Using immunohistochemistry for CD34, we assessed vascular patterns in 114 primary glioblastomas. Vascular patterns comprised unevenly distributed glomeruloid/garland-like/clustered bizarre vascular formations and evenly distributed delicate capillary-like microvessels ("classic" vascular pattern). The combination of low content of bizarre vascular formations and prominent classic vascular pattern (n=29) was an independent factor for longer survival (p= 0.006, Cox regression), as well as postoperative high Karnofsky performance status (p=0.005). In patients with a prominent classic vascular pattern, there was no difference of MIB1 labeling index whereas microvessel density and apoptotic index (TUNEL) were significantly higher as compared to all other patients (p<0.05). In addition, diffuse expression of hypoxia-inducible factor (HIF)-1, and strong expression of vascular endothelial growth factor were more common (p<0.05, Chi-square test). FISH revealed loss of chromosomes 1p and 19q only in 1/7 long-time survivors with classic pattern. We conclude that vascular patterns in primary glioblastoma influence clinical outcome and associate with variable expression of angiogenic proteins. Our findings denote for the first time distinct angiogenic subtypes of human glioblastoma which may prove relevant for anti-angiogenic therapy approaches. [source] | |||||||||||||