Showing papers on "Vascular endothelial growth factor A published in 1979"

An endothelial cell growth factor from bovine hypothalamus: identification and partial characterization.

Abstract: Extracts of bovine hypothalamus were found to contain a significant level of mitogenic activity when tested in a Swiss 3T3 cell [3H]dThd incorporation assay and in a human umbilical vein endothelial cell growth assay. The mitogenic activity responsible for 3T3 cell activity was purified and characterized as a fibroblast growth factor (FGF)-like mitogen. Neither the biologically active FGF-like mitogen purified from the hypothalamus extracts nor FGF purified from bovine pituitary glands was mitogenic when added to human endothelial cells in vitro, suggesting the presence of more than one mitogen in the hypothalamic extracts. The 3T3 and endothelial cell biological activities of hypothalamic extracts were both found to be inactivated by trypsin, subtilisin, and heat treatment, but were stable to dialysis. The endothelial cell growth factor activity could be efficiently separated from the FGF activity by gel exclusion chromatography. The endothelial cell mitogen possessed a molecular weight of approximately 75,000, whereas that of FGF was approximately 15,000. The endothelial cell growth factor activity was found to be inactivated with reducing agents whereas the 3T3 cell mitogenic activity was stable after incubation with 2-mercaptoethanol. Significant levels of endothelial cell mitogenic activity were also found in extracts of bovine brain and pituitary glands.

Vascular endothelial and smooth muscle cells in culture selectively release adenine nucleotides

Abstract: Endothelial cells in culture can modulate platelet aggregation and vascular tone, in part by producing prostacyclin (PGI2)1,2, a powerful vasodilator and inhibitor of platelet aggregation3,4, but also by their ecto-ADPase activity5, which initiates the conversion of pro-aggregating ADP to adenosine, a potent vasodilator6 and platelet inhibitor7. We have now demonstrated that cultured aortic endothelial cells exposed to trypsin, thrombin or other stimuli can liberate a high proportion of their adenine nucleotides without substantial loss of lactate dehy-drogenase. ADP rapidly accumulates extracellularly, reaching biologically active concentrations before there is further breakdown to adenosine. Whether this selective release of nucleotides is a response to damage, or whether it represents a specific secretory mechanism remains to be resolved. Cultured aortic smooth muscle cells can secrete adenine nucleotides in a similar manner, but extracellular conversion to adenosine occurs much faster.

Human beta-thromboglobulin inhibits PGI2 production and binds to a specific site in bovine aortic endothelial cells.

Abstract: Blood platelets have a major role in haemostasis through their aggregation and adherence to the damaged vessel wall During this process, platelet granular constituents are released Although the functions of many of these release products are well known, biological functions of some well defined platelet specific proteins have not been determined This category includes platelet factor 4 (PF4) and β-thromboglobulin (βTG), both small proteins of molecular weight 30,000–36,000 (refs 1, 2) which are stored in the α granule of the platelet and have not been detected in any other tissue βTG is composed of four identical noncovalently bound subunits and its amino acid sequence is significantly homologous with that of PF4 (ref 3) Although PF4 possesses a marked ability to neutralise heparin, no physiological or pathophysiological role has been attributed to either protein The discovery of prostacyclin (PGI2) has led to a reappraisal of the factors regulating haemostasis and especially of the role of the vascular endothelium in preventing platelet adherence and aggregation4–6 The initial action of PGI2 on the platelet is to stimulate adenylate cyclase7–9, and it is the most potent inhibitor of platelet aggregation yet discovered Also, cultures of arterial and venous endothelial cells have been found capable of producing PGI2 (refs 10,11) We now report results indicating that βTG reduces the production of PGI2-like activity in cultured bovine endothelial cells, which are shown to possess a specific receptor for βTG The characteristics of this receptor suggest that βTG may act locally at high concentrations to favour platelet aggregation by diminishing PGI2 production

Structural and functional alterations in the surface of vascular endothelial cells associated with the formation of a confluent cell monolayer and with the withdrawal of fibroblast growth factor

Abstract: Vascular endothelial cells cultured in the presence of fibroblast growth factor (FGF) divide actively when seeded at low or clonal cell densities and upon reaching confluence adopt a morphologic appearance and differentiated properties similar to those of the vascular endothelium in vivo. In this review, we present some of our recent observations regarding the characteristics (both structural and functional) of these endothelial cells and the role of FGF in controlling their proliferation and normal differentiation. At confluence the endothelial cells form a monolayer of closely apposed and nondividing cells that have a nonthrombogenic apical surface and can no longer internalize bound ligands such as low-density lipoprotein (LDL). The adoption of these properties is correlated and possibly causally related to changes in the cell surface such as the appearance of a 60,000 molecular weight protein (CSP-60); the disappearance of fibronectin from the apical cell surface and its concomitant accumulation in the basal lamina; and a restriction of the lateral mobility of various cell surface receptor sites. In contrast, endothelial cells that are maintained in the absence of FGF undergo within three passages alterations that are incompatible with their in vivo morphologic appearance and physiologic behavior. They grow at confluence on top of each other and hence can no longer adopt both the structural (CSP-60, cell surface polarity) and functional (barrier function, nonthrombogenicity) attributes of differentiated endothelial cells. Since these characteristics can be reacquired in response to readdition of FGF, in addition to being a mitogen FGF may also be involved in controlling the differentiation and phenotypic expression of the vascular endothelium.

Estrogen-Binding Sites In Endothelial Cell Cultures

Abstract: The cytosol extracted from a vascular endothelial cell line binds [3H]estradiol with high affinity and a high degree of specificity. In contrast, in experiments performed with cytosol labeled in the intact cell, progesterone and, to a smaller extent, testosterone gave an apparent inhibition of estradiol binding. These data support the concept that ovarian hormones may influence the role of the endothelium in various physiological and pathophysiological conditions.

A variant vascular endothelial cell line with altered growth characteristics.

Abstract: A variant endothelial cell type was found to arise spontaneously from cultures of bovine aortal endothelial cells. This variant showed no contact inhibition and overgrew confluent cultures of wild-type endothelial cells. Unlike other reported variants of this cell type produced by chemical mutagenesis or by withdrawal of polypeptide growth factor, this variant retained the capacity to synthesise factor VIII antigen, but showed no alteration from wild-type in capacity to adsorb platelets. The variant also had an increased capacity to bind FITC-conjugated con A to its surface.