scispace - formally typeset
Search or ask a question

Showing papers on "Vascular endothelial growth factor A published in 1984"


Journal ArticleDOI
TL;DR: The endothelium-dependent relaxation by each of these agents was shown to be preceded by an endothelia-dependent increase in cyclic GMP in the smooth muscle--a finding consistent with the hypothesis that EDRF stimulates guanylate cyclase in the muscle, leading to an increase in cycling GMP that somehow activates relaxation.
Abstract: Summary:A brief review is first presented of findings during the past few years by the authors and by others on the nonprostaglandin endothelium-dependent relaxation of isolated arteries by a large number of vasoactive agents. Among these agents are acetylcholine (ACh); the calcium ionophore A23187;

320 citations


BookDOI
01 Jan 1984
TL;DR: In vitro systems for studying the interaction of metastatic tumor cells with endothelial cells and subendothelial basement membranes and the metabolism of vasoactive peptides by human endothelium are studied.
Abstract: Tissue Culture of Endothelial Cells.- Culture and identification of large vessel endothelial cells.- Culture of capillary endothelial cells.- Culture of endothelial cells from neural capillaries.- Culture of pulmonary endothelial cells on microcarrier beads.- Construction of an artificial blood vessel wall from cultured endothelial cells.- Determinants of Endothelial and Smooth Muscle Cell Growth.- Growth requirements for bovine aortic endothelium in vitro.- Contact inhibition in the endothelium.- Endothelial cell motility.- Factors which stimulate the growth of human umbilical vein endothelial cells in vitro.- Macrophages, neovascularization, and the growth of vascular cells.- The limited life-span of bovine endothelial cells.- Endothelium, heparin, and the regulation of vascular smooth muscle cell growth.- Morphology of Cultured Endothelial Cells.- Morphology of vascular endothelial cells in culture.- The endothelial cytoskeleton.- Synthesis of Connective Tissue Elements by Endothelial Cells.- Metabolism of thrombospondin and fibronectin by endothelial cells.- Collagen synthesis by endothelial cells in culture.- Sulfated glycosaminoglycans and vascular endothelial cells.- Elastin synthesis by endothelial cells.- Gene mapping using hybrids of human endothelial cells and rodent fibroblasts.- Interactions of Endothelial Cells with the Coagulation and Complement Systems and Formed Elements in Blood.- Properties of plasminogen activators produced by endothelial cells.- Synthesis of Factor VIII by endothelial cells.- Tissue factor activity of cultured human vascular cells.- Activation of Hageman factor by cultured rabbit endothelial cells.- Prostacyclin production by endothelial cells.- Regulation of endothelial cell function by cyclic nucleotides.- Interactions of thrombin, antithrombin III, and Protein C with endothelium.- Viral infection of endothelium and the induction of Fc and C3 receptors.- Adhesive interactions between polymorphonuclear leukocytes and endothelium.- Neutrophil endothelial interactions.- Synthesis of colony stimulating activity by endothelial cells.- Interaction with and Metabolism of Plasma Components by Endothelial Cells.- The metabolism of vasoactive peptides by human endothelial cells.- The metabolism of angiotensin I and bradykinin by endothelial cells.- Metabolism of serotonin and adenosine.- Receptors for insulin and multiplication stimulating activity (MSA) in endothelial cells.- Binding of lipoprotein lipase to cultured endothelial cells.- Role of lipoproteins in the regulation of cultured endothelial cell cholesterol metabolism.- Quantitative aspects of endocytosis in cultured endothelial cells.- Immunologic Aspects of Endothelial Cells.- The alloantigens of endothelial cells.- Accessory cell function of human endothelial cells: presentation of antigen to T cells.- Cell surface markers on endothelial cells: a developmental perspective.- Endothelial Cell and Vasular Prostheses.- Endothelial seeding of vascular prostheses.- Endothelial Cells and Cancer.- Angiogenesis.- Synthesis of collagenase and plasminogen activator by endothelial cells.- In vitro systems for studying the interaction of metastatic tumor cells with endothelial cells and subendothelial basement membranes.

249 citations



Journal ArticleDOI
TL;DR: It is suggested that thrombomodulin and Factor Va act in concert to regulate protein C activation on the surface of endothelial cells.
Abstract: In vitro the rate of protein C activation by thrombin is significantly accelerated by two distinct cofactors (a) the endothelial cell surface protein, thrombomodulin, and (b) human coagulation Factor Va. We have recently reported that the activity of Factor Va is contained in the 78,000-D light chain. In this study we have investigated the effects of Factor Va and its light chain on the activation of protein C in the presence of cultured endothelial cells. Thrombin-catalyzed protein C activation on human umbilical vein endothelial cells was enhanced by Factor Va. The ability of Factor Va to stimulate protein C activation on these cells was saturated at 50 nM Factor Va and was observed at several protein C concentrations. Isolated Factor Va light chain in concentrations up to 50 nM also accelerated protein C activation on endothelial cells, but higher concentrations inhibited the reaction. The effects of Factor Va or its light chain on protein C activation were also shown on a mouse hemangioma cell line but not on human fibroblasts nor on a human amelanotic melanoma cell line. Protein C activation on endothelial cells was partially inhibited by a goat anti-thrombomodulin antibody and further addition of a polyclonal rabbit anti-Factor V(Va) antibody resulted in additional inhibition. Endothelial cells grown in medium supplemented with human serum, devoid of Factor V coagulant activity, contained cell surface Factor V(Va) (approximately 15,000 molecules/cell) as measured by the binding of a monoclonal IgG directed against Factor V(Va). These cells also bound an additional 6,000-10,000 molecules Factor Va per cell as determined by direct binding studies using 125I-Factor Va. We suggest that thrombomodulin and Factor Va act in concert to regulate protein C activation on the surface of endothelial cells.

78 citations


Journal ArticleDOI
TL;DR: Human glomerular endothelial cells have been isolated, cloned, and characterized and demonstrated high levels of membrane-associated angiotensin-converting enzyme (ACE), which was also a requirement for continuous growth.
Abstract: Human glomerular endothelial cells have been isolated, cloned, and characterized. They appeared as the first outgrowth from human glomeruli in the presence of platelet-derived growth factor, which was also a requirement for continuous growth. By phase microscopy they appeared as monolayers of polygonal cells. Von Willebrand's factor (VWF) was detected in the cytoplasm of all clones. Their intermediate filaments differed antigenically from that present in human umbilical vein endothelial cells. Like other endothelial cells, they demonstrated high levels of membrane-associated angiotensin-converting enzyme (ACE).

67 citations


Journal ArticleDOI
01 Mar 1984-Blood
TL;DR: It is demonstrated that endothelial cells produce proteins of approximately 30,000 daltons, with isoelectric focusing points of 4.5 and 7.2, which stimulate the growth of human BFU-E and CFU-mix, which suggests that endotheric cells play an active role in the modulation of human hematopoietic stem cell growth.

62 citations


Journal ArticleDOI
TL;DR: Optimal conditions for long-term culture of effector cells from mixed leukocyte endothelial cell cultures were analyzed and addition of II 2 every 3 days and the original stimulating antigen every 6 days permitted continuous proliferation of these cytotoxic lymphocytes with preservation of the cytotoxicity pattern.
Abstract: Data are presented on the ability of arterial and venous endothelial cells to stimulate allogeneic leukocytes. Mixed cultures of allogeneic endothelium and lymphocytes result in proliferation of lymphocytes and generation of cell-mediated cytotoxicity, which do not occur in cultures of syngeneic combinations of endothelium and lymphocytes. Studies of kinetics showed a peak in proliferation at days 6-7. The optimal responder-stimulator ratio appeared to be 15:1. Lymphocytes stimulated with venous endothelial cells were cytotoxic both for arterial and for venous endothelial cells and PHA blasts of the stimulator dog, whereas lymphocytes stimulated with arterial endothelial cells lysed only arterial endothelial cells and PHA blasts of the stimulator. Lysis of syngeneic or third-party allogeneic control targets was virtually absent. Optimal conditions for long-term culture of effector cells from mixed leukocyte endothelial cell cultures were analyzed. Addition of Il 2 every 3 days and the original stimulating antigen every 6 days permitted continuous proliferation of these cytotoxic lymphocytes with preservation of the cytotoxicity pattern.

16 citations


Journal ArticleDOI
TL;DR: To clarify the mechanism of the centrosomal orientation response, preincubated the monolayers in DMEM containing drugs known to have specific actions, and observed the response 5 min after simultaneous wounding and exposure to each growth factor and energy inhibitors blocked the response.
Abstract: Endothelial cells (ECs) lining the inner wall of arteries migrate as a result of injury to the blood vessel. This EC locomotor response, which plays an important role in the mechanism of wound healing and the etiology of atherosclerosis and diabetic vascular complications, is associated with rapid changes in cell shape and the state of the cytoskeletal frame. Recently, Gotlieb et al.’ showed that the centrosome, a major microtubule-organizing center, translocates around the nucleus to position itself between the nucleus and the wound track in porcine aortic ECs bordering an experimental, linear wound. This response to injury was associated with cell orientation and locomotion into the wound. It was, therefore, relevant to determine whether this intracellular process was mediated by specific humoral factors. A primary culture of bovine aortic ECs was grown on 12-mm coverslips in Dulbecco’s modified Eagle medium (DMEM) with 10% calf serum to confluence, and serum-deprived for 3 6 4 8 hr. Serum-deprived EC monolayers were wounded in a linear fashion with the tip of a metal spatula. One hundred microliters of growth factor or DMEM was added at various times and concentrations to the wounded monolayers. After incubation, the cells were fixed with absolute methanol and processed for immunofluorescence to localize the centrosome and microtubules.* Under a Zeiss microscope, centrosomal orientation was classified as positive (facing the wound) or negative (away from the wound) in 10G150 cells bordering the wound (FIGURE 1). Results were expressed as the mean percentage of cells with their centrosome oriented toward the wound. Variability between replicate counts was 6% or less. By adding specific growth factors on wounding and fixing the cells 15 min later, we observed that fetal bovine serum (FCS, 10%). insulin, or Multiplication Stimulating Activity (MSA) induced a positive response in >70% of border cells. DMEM, glucagon, Platelet-Derived Growth Factor, and Fibroblast Growth Factor did not affect random centrosomal orientation (50%). Using optimal concentrations of insulin M), MSA (100 ng/ml), and FCS (lo%), we observed that the growth factor-mediated response occurred within a fraction of a minute and persisted for a t least 30 min after simultaneous wounding and exposure to each growth factor (TABLE 1). To clarify the mechanism of the centrosomal orientation response, we preincubated the monolayers in DMEM containing drugs known to have specific actions, and observed the response 5 min after simultaneous wounding and exposure to each growth factor. We observed that energy inhibitors such as dinitrophenol and sodium fluoride blocked the response. Drugs that either stimulated disassembly (Colcemid) or induced disorganized assembly (Taxol) of microtubules also blocked the response. Phalloidin, which stabilizes microfilaments, blocked the effect of growth factors; cytochalasin D, which disassembles microfilaments, blunted the response (60 vs. 70%). a calcium ionophore, stimulated the response alone and did not interfere with the growth

5 citations



Journal ArticleDOI
01 Jan 1984-Nephron
TL;DR: It is observed, using immunofluorescence microscopy and a nucleic acid counterstain with ethidium bromide, that in the normal human kidney HLA-DR antigens are localized on the vascular endothelium around cellular structures.
Abstract: P. Arrizabalaga, MD, Servicio de Nefrología, Hospital Clínico, c/Casanova, 143, E-Barcelona 36 (Spain) Dear Sir, Human HLA-DR antigens are expressed on cytoplas-mic membrane of cells associated with immunological activity [1]. Moreover, the HLA-DR expression can be induced on other cells which are normally negative for HLA-DR molecules. Thus, the thyroid follicular cells bear these antigens when cultured with mitogens [2]. The umbilical vein endothelial cells express HLA-DR when cultured with phytohemagglutinin [3] or co-cultured with activated T cells [4]. Häyry et al. [5] observed HLA-DR antigens on the dispersed kidney vascular endothelial cells. In addition, morphological studies on tissue sections suggest that renal vascular endothelium appears to express HLA-DR antigens [6–8]. We have observed, using immunofluorescence (IF) microscopy and a nucleic acid counterstain with ethidium bromide (EB), that in the normal human kidney these antigens are localized on the vascular endothelium around cellular structures. We have used a mouse monoclonal antibody directed against a monomorphic determinant of HLA-DR (Edu-1) described elsewhere [9, 10]. Normal renal tissue from 2 biopsy and 9 necropsy specimens was tested for HLA-DR antigens by indirect IF technique. A nucleic acid stain with EB was used for cellular localization. Tonsil sections were used as positive control. Monoclonal antibody to non-HLA-DR antigens (Cris-1) [9,11] and ascitic fluid, obtained intraperitoneally of Balb/c NSA myeloma line were used as negative controls. A constant pattern of HLA-DR antigens was observed in all the specimens. Heavy IF staining was identified in the renal interstitium and in the glomerular capillary walls. Moreover, bright staining was observed in the mesan-gium. EB counterstaining showed HLA-DR antigens around endothelial cells in glomerular capillaries (fig. la) and probably vascular endothelial cells in intertubular capillaries (fig. lb). The considerable amount of HLA-DR antigens observed in capillaries of human normal kidney suggest at least two biological implications. First, the vulnerability of the microcirculation of transplanted kidney to circulating antibodies with specificity for HLA-DR antigens

1 citations