Showing papers on "Vascular endothelial growth factor A published in 1985"

Pure brain-derived acidic fibroblast growth factor is a potent angiogenic vascular endothelial cell mitogen with sequence homology to interleukin 1.

Abstract: Pure bovine brain-derived acidic fibroblast growth factor is a very potent mitogen for vascular endothelial cells in culture and, in the presence of heparin, induces blood vessel growth in vivo. Partial amino acid sequence determinations confirm that this mitogen is a unique protein having amino acid sequence homology with human interleukin 1.

Cultured human endothelial cells express platelet-derived growth factor B chain: cDNA cloning and structural analysis

Abstract: Vascular endothelial cells have a central role in various pathophysiological responses such as acute inflammation, wound healing and atherogenesis. The anatomical position of endothelial cells between blood leukocytes and the surrounding vascular smooth muscle cells or stromal fibroblasts may intensify and focus the effects of released endothelial cell products. Endothelial cells in culture produce a platelet-derived growth factor (PDGF)-like mitogen1. PDGF purified from platelets is a basic protein with an apparent relative molecular mass (Mr) of ∼30,000 (reviewed in refs 2, 3) and is believed to comprise two polypeptide chains, PDGF-A and PDGF-B4 (also referred to as PDGF-1 and PDGF-2; refs 5, 6). Sequence analysis of PDGF B chain has revealed a striking homology with the predicted sequence of p28sis, the transforming protein of simian sarcoma virus4,6,7, sis-Homologous transcripts have been detected by Northern blot analysis of RNA from cultured endothelial cells8. However, there are no structural data available on either the protein product or the messenger RNA to establish the identity of the endothelial-derived mitogen with either chain of PDGF. Here we report the isolation and complete sequence analysis of a sis-homologous complementary DNA clone from human endothelial cells, providing an opportunity to study the structure of sis as transcribed by a normal (untransformed) cell. Our results establish that normal human endothelial cells in culture express the B chain of PDGF, and that endothelial-derived PDGF B chain is synthesized as a predicted precursor polypeptide of Mr 27,281.

An endothelial cell-dependent pathway of coagulation

Abstract: Although the endothelial cell is considered antithrombogenic, endothelium has recently been shown to participate in procoagulant reactions. In this report cultured bovine aortic endothelial cells are shown to propagate a procoagulant pathway starting with factor XIa, leading to activation of factors IX, VIII, X, and prothrombin, culminating in fibrinopeptide A cleavage from fibrinogen and formation of a fibrin clot. Electron microscopic studies demonstrated that fibrin strands are closely associated with the endothelial cells. Endotoxin-treated endothelial cells, having acquired tissue factor activity, generated fibrinopeptide A in the presence of factors VIIa, IX, VIII, X, prothrombin, and fibrinogen. Factor X activation by factor VIIa and tissue factor expressed by endothelial cells is 10 times greater in the presence of factors IX and VIII than in their absence. This indicates that on the perturbed endothelial cell surface, factors IX and VIII do have an important role in the activation of factor X. Addition of platelets (10(8) per ml) augmented thrombin formation seen in the presence of endothelium alone by about 15-fold. Anti-human factor V IgG decreased this enhanced thrombin formation in the presence of platelets, indicating that factor V from platelets was playing an important role in thrombin formation. These data lead us to propose that endothelial cells can actively participate in procoagulant reactions. Although platelets can augment thrombin formation by these endothelial cell-dependent reactions, endothelial cells alone can lead to formation of a cell-associated fibrin clot. The endotoxin-treated endothelial cell provides a model of the thrombotic state supplying tissue factor to initiate coagulation and propagating the reactions leading to fibrin formation. This endothelial cell-dependent pathway suggests a central role for factors VIII and IX consistent with their importance in hemostasis.

Physiologic Functions of Normal Endothelial Cells

Abstract: Endothelial cells (EC) line the insides of all blood vessels and occupy a surface area of more than 1000 m2. Assuming individual endothelial cells are approximately 20 x 50 microns’, the body contains about 1000 m’/1000 microns’ or 10” endothelial cells which weigh in excess of 100 grams. Because of their location and contact with the flowing bloodstream, endothelial cells are perfectly positioned to modulate the various biologic systems in blood, particularly the coagulation system. The development in the early 1970’s of methods for culturing EC‘ made possible the study of EC cell biology. In this article, I will review briefly the normal physiologic functions of EC.

Partial purification and characterization of a vascular permeability factor secreted by a human colon adenocarcinoma cell line.

Abstract: The established human colon adenocarcinoma cell line, HT-29, secretes a vascular permeability factor (VPF) in vitro. The factor has been purified from serum-free conditioned medium by acidification, cation-exchange, and reverse-phase and anion-exchange high-performance liquid chromatography. The VPF is a non-glycosylated acidic protein of apparent molecular weight 45,000, and is at least 4 orders of magnitude more potent than histamine as an inducer of vascular permeability. Its biological activity is unaffected by soybean trypsin inhibitor or by inhibitors of histamine, kinins, prostaglandins, or acid proteases. The VPF induces vascular permeability within minutes, which suggests a direct effect on the endothelial cell.

Influence of anti-endothelial cell antibodies on the interactions of leukocytes with vascular endothelial cells in vitro.

Abstract: The role of mononuclear cells in antibody-mediated endothelial cell damage and vascular diseases is not well understood when compared to our understanding of the role of neutrophil-mediated endothelial injury in vascular diseases. Thus we initiated these in-vitro studies to investigate the interactions of leukocytes (neutrophils and mononuclear cells) with vascular endothelial cells in the presence and absence of antiendothelial cell antibodies (anti-red blood cell antiserum-anti-RBC). Cultured endothelial cells were isolated from bovine pulmonary artery. The effects of unfractionated and fractionated human leukocytes (neutrophils, mononuclear cells, or lymphocytes) on endothelial cell viability was examined both quantitatively (51Cr release) and qualitatively (electron microscopy). Results from these studies indicated that the interactions of mononuclear cells and lymphocytes with antibody-coated endothelial cells resulted in a significant endothelial cell lysis within 1 to 6 hours of reactions. Neutrophils, on the other hand, failed to induce significant endothelial cell damage compared to mononuclear cells and lymphocytes when tested under similar conditions. In the absence of anti-RBC antibodies, all cell types (neutrophils, mononuclear cells, or lymphocytes) did not produce detectable endothelial damage. Additionally, the effectiveness of mononuclear cells to injure antibody-labeled endothelial cells was confirmed by ultrastructural examination. Similar studies, utilizing leukocytes obtained from patients with atherosclerosis disease, were also undertaken. In these studies we found that, again, only mononuclear cells and lymphocytes wer capable of inducing damage to endothelial cells precoated with antibodies. In summary, our results demonstrate the ability of mononuclear cells and lymphocytes to induce significant damage to antibody-coated endothelial cells. This finding suggests a major role of mononuclear leukocytes in vascular endothelial destruction in diseases that are characterized by the presence of circulating autoantibodies in serum and the adhesion of mononuclear cells to the vascular wall. Such diseases include vasculitis, allograft rejection, serum sickness, and perhaps atherosclerosis particularly in patients with autoimmune diseases.

Augmentation by heparin of endothelial cell proliferation in vitro

Abstract: Regulatoy effect of heparin on the growth of porcine aortic endothelial cells was examined. Heparin did not stimulate the growth of endothelial cells by itself, while it potentiated the effect of endothelial cell growth factor (ECGF) from bovine brain. In the presence of ECGF, heparin stimulated the growth of endothelial cells in a dose-dependent manner, and protamine neutralized the effect of heparin. Other glycosaminoglycans such as heparan sulfate and dermatan sulfate had no effect on endothelial cell growth. Affinity chromatography on a heparin-Sepharose column has shown that ECGF has a strong affinity for heparin. These observations suggest that heparin binds specifically to ECGF and thus influences the growth of endothelial cells.

Biochemical characterization of vascular endothelial cell proliferation factor derived from human platelets

Abstract: Human platelets are known to enhance the proliferation of vascular endothelial cells in vitro. In order to identify the responsible factor, a platelet factor stimulating the growth of endothelial cells was isolated and characterized. Isoelectric focusing revealed that a pI of the factor is 4.0-4.8. Gel exclusion chromatography showed at least two peaks of activity on endothelial cells, the major peak being at an apparent molecular weight of 20, 000. Growth-promoting activity on endothelial cells was inactivated by heat, trypsin or 1M acetic acid, but was resistant to reducing agents. This platelet factor is a heat- and acid-labile anionic polypeptide that preferentially stimulates the growth of vascular endothelial cells.