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At least 37 records · Page 2Linked to original sources
PubMed1979

Effect of thrombin on the fibrinolytic activity of cultured bovine endothelial cells.

The vascular endothelium is a rich source of plasminogen activator (PA) and thus of blood vessel-associated fibrinolytic activity. Cultured bovine aortic endothelial cells were employed to determine if components of the coagulation system interact with the endothelium to modify expression of this activity. The addition of thrombin to these cultures led to a rapid decline in intracellular PA activity, with as little as 3 ng/ml, or 0.1 nM thrombin causing a 50% decrease within 30 min. Thrombin inactivated with diisopropylflurophosphate or hirudin did not elicit the response. Although control cultures secreted high levels of PA, no PA activity could be detected in the media surrounding the thrombin-treated cells. This loss of activity did not appear to result from direct inactivation of PA by thrombin. These observations indicate that the fibrinolytic potential of cultured endothelial cells is rapidly suppressed by trace amounts of thrombin. The generation of thrombin at sites of vascular injury may have a similar effect on the endothelium.

Animals↗
PubMed1977

Synthesis of a fibrinolytic activator and inhibitor by endothelial cells.

Vascular endothelial cells derived from rabbit vena cava and maintained in continuous culture exhibited properties characteristic of the intact endothelium. These cells were used as a model for characterizing the fibrinolytic components specified by the endothelium. Endothelial cells in culture digested radiolabeled fibrinogen. Digestion resulted from the synthesis and secretion of a plasminogen activator. Fibrinolysis was not detected when cells were grown in medium lacking plasminogen, indicating the absence of plasminogen-independent fibrinolytic enzymes. Phorbol-myristate-acetate increased extracellular plasminogen activator activity dramatically. This increase was prevented when actinomycin D or cycloheximide was included in the growth medium, indicating that new gene expression was required for it. Intracellular plasminogen activator could not be detected unless the cell extracts were exposed briefly to mildly acidic conditions. Mixing experiments between acid-treated and untreated extracts suggested that the cells contained a potent, acid-labile inhibitor of fibrinolysis. As little as 10 mug of protein from whole cell extracts inhibited both cell and urokinase-mediated fibrinolysis by more than 70%. Cell fractionation studies localized the inhibitor to the cytosol whereas plasminogen activator activity was restricted to the membrane-rich fraction. This membrane fraction did not require acidification for activity, suggesting that the inhibitor had been removed and that acidification did not activate a plasminogen proactivator. These observations demonstrate that regulation of endothelial fibrinolytic activity is far more complex than had been anticipated and raise several uncertainties in regard to detecting the presence of plasminogen activators in cells and tissues.

Animals↗
PubMed1979

Studies on end-stage kidneys. V. Unusual epithelial activity or remarkable endothelial metaplasia. Findings in a dialyzed kidney.

Tubule-like cells were found lining an artery and several arterioles and within the capillaries of infarcted glomeruli in one block of kidney from one of 54 cases of end-stage/dialysis kidneys. Three other blocks showed tubule-like structures within infarcted glomeruli and adjacent arterioles. Squamous metaplasia of remaining tubule epithelium was found in sections from four blocks of the same kidney. In two of these blocks, infarcted glomeruli had capillaries which were occupied by squamous cells. These findings are discussed as examples of metaplasia of the endothelium or alternatively as epithelial growth and invasion. The use of special stains and multiple blocks for this study seem to have been justified. These changes offer further evidence that the end-stage kidney after dialysis has unique alterations.

Adult↗
PubMed1979

The effect of cultured endothelial cells on factor VIII procoagulant activity.

Cultured human umbilical vein endothelial cells produce a protein that has von Willebrand factor activity and forms immunoprecipitates with rabbit antibody to purified plasma factor VIII/von Willebrand factor (FVIII/vWF) protein, but it has no FVIII procoagulant activity. Of the three characteristics of plasma FVIII/vWF protein, only FVIII procoagulant activity is readily destroyed by trace proteases. A previous report from this laboratory demonstrated protease activity in culture medium under conditions that had been used by others to show that endothelial cells do not synthesize protein with FVIII procoagulant activity. However, even if cultured endothelial cells are placed in protease-free culture medium, no FVIII procoagulant activity can be detected, despite an increase in the level of protein with vWF activity from 0 to 0.57 microgram/ml by 48 hr. This observation and the lack of protease activity in medium left in contact with the cells for 48 hr led to the hypothesis that proteases exist on the surface of cultured umbilical vein endothelial cells. Protease activity was quantitated by the hydrolysis of p-nitroaniline from the substrate, N-benzoyl-phenylalanyl-valyl-arginyl-p-nitroanilide and by degradation of the procoagulant activity of added purified plasma FVIII/vWF protein. In the absence of endothelial cells, no protease activity was present in protease-free culture medium whether or not it had previously overlaid cultured cells. This medium did not cause cleavage of p-nitroaniline from the tripeptide substrate, and 83% of added FVIII procoagulant activity remained after 48 hr. When the synthetic tripeptide was incubated in contact with cultured endothelial cells, 7.3 +/- 0.8 X 10(-10) moles of p-nitroaniline/hr was released; moreover, only 47% of the added FVIII procoagulant activity remained after 48 hr. Given this rate of destruction, it can be calculated that sufficient protease activity exists on the surface of cultured endothelial cells to degrade the procoagulant activity of approximately 1.6 microgram FVIII/vWF protein/hr. This degradation rate is 45 times the rate of release of FVIII/vWF protein from cultured endothelial cells when assessed by the generation of protein with vWF activity. Hence, the detection of FVIII procoagulant activity, if in fact synthesized by cultured endothelial cells, will be most difficult.

Cells, Cultured↗
PubMed1978

Comparative pharmacologic effects on tissue factor activity in normal cells and an established cell line.

The tissue factor (thromboplastin) activity of cells grown in vitro is modulated by exogenous drugs. The activity of human foreskin fibroblasts and umbilical vein smooth muscle cells is enhanced by 10(-6) M hydrocortisone or 1 mM butyrate. Activity is suppressed in these cells by 10(-6) M colchicine whereas 10(-4) M chloroquine has little or no effect. Two established cell lines, WISH or HeLa cells, have elevated tissue factor activity in the presence of colchicine or chloroquine and suppressed activity with exogenous hydrocortisone. Their activity is also decreased by 10 mM butyrate whereas 1 mM butyrate does not alter activity. Colchicine and butyrate apparently act via a mechanism unrelated to their effect on microtubules since it is possible to dissociate activity changes from morphologic changes. Umbilical vein endothelial cell tissue factor activity responds uniquely to exogenous drugs. Hydrocortisone or 10(-5) M vinblastine (or colchicine) only minimally alters activity. Endothelial cells are not simply refractory toward all drugs, however, since chloroquine dramatically enhances activity whereas 1 mM butyrate suppresses it. The low specific activity of endothelial cells and their apparently unique drug response may be another measure of their function as an in vivo hemostatic barrier.

Amnion↗
PubMed1979

Granulocyte aggregation as a manifestation of membrane interactions with complement: possible role in leukocyte margination, microvascular occlusion, and endothelial damage.

Activation products of the terminal complement cascade potently affect granulocyte function, inducing, for example, their migration toward (chemotaxis), and adherence to (opsonization), microbes, and stimulating their production of microbicidal oxygen radicals such as superoxide anion, and the like. We present studies that demonstrate that a C5-derived peptide, probably C5a, is a potent promoter of granulocyte and monocyte adhesion to endothelium (margination) and, in addition, causes granulocyte autoaggregation in vitro and in vivo. Although possibly beneficial by producing phagocyte clumps to mechanically entrap unwanted microbes, such aggregates may be deleterious, particularly if sustained, especially in the lung.

Animals↗
PubMed1978

Regions of constantly increased plasminogen activator activity along the intima of the normal aorta.

Histochemical studies of the aorta in newborn, young, and adult rats showed that the intima in the branching regions and at the beginning of the branches has a constantly increased plasminogen activator activity in comparison with the nonbranching regions. The aortic valve also shows constantly increased activator activity. The intimal activator activity is variable in the nonbranching regions, depending on the age and the anatomical area of the aorta. In young rats (20--30 days), the overall plasminogen activator activity in the aortic intima is higher than in adult rats (2--4 months), while the activity is variable in newborn rats. The intimal activator activity is generally higher in the thoracic aorta than in the abdominal aorta (in the nonbranching regions). The aortic wall has a low plasmin inhibitor capacity. The pattern of the endothelial plasminogen activator activity at different ages and anatomical areas of the aorta, in combination with the corresponding pattern of the aortic endothelial cell turnover, gives valuable information about the mechanism(s) of the production and normal (nonstressed) release of the endothelial plasminogen activator.

Aging↗
PubMed1977

Metabolism of vasoactive peptides by human endothelial cells in culture. Angiotensin I converting enzyme (kininase II) and angiotensinase.

Cultured endothelial cells provide a model for the study of interactions of vasoactive peptides with endothelium. Endothelial cell cultured from veins of human umbilical cords contain both angiotensin I converting enzyme (kininase II) and angiotensinase activities. Intact monolayers of cells can both activate angiotensin I and inactivate bradykinin when the peptides are added to culture flasks in protein-free medium. Intact suspended cells or lysed cells convert angiotensin I to angiotensin II, inactivate bradykinin, and hydrolyze hippuryldiglycine to hippuric acid and diglycine. These actions are inhibited by SQ 20881, the specific inhibitor of converting enzyme. The kininase activity of endothelial cells was partially inhibited by antibody to human lung converting enzyme. Endothelial cells also inactivate longer analogs of bradykinin, such as kallidin, methionyl-lysyl bradykinin, and bradykinin coupled covalently to 500,000 mol wt dextran. The endothelial cells retained converting enzyme activity through four successive subcultures, indicating that the enzyme is synthesized by the cells surface, and it is apparently a marker for endothelial cells, since cultured human fibroblasts, smooth muscle cells, and baby hamster kidney cells do not have it. Endothelial cells also contain an aminopheptidase which hydrolyzes both angiotensin II and the synthetic substrate, alpha-L-aspartyl beta-naphthylamide. The angiotensinase activity increased when the cells were lysed, which suggests that the enzyme is localized within the cells, Hydrolysis of both alpha-L-aspartyl beta-naphthylamide and angiotensin II was inhibited by omicron-phenanthroline, indicating that the enzyme is an A-tipe anigotensinase.

Angiotensin II↗
PubMed1977

The role of lysosomal enzymes in protein degradation in different types of rat liver cells.

Highly purified suspensions of parenchymal, endothelial and Kupffer cells were prepared from the rat liver. The respective roles of these cell classes in the degradation of proteins was investigated by analysing the cellular distribution of two lysomal proteases. The specific arginine naphthylamidase activity was 2 times higher in Kupffer cells compared with the nearly equal activities in endothelial and parenchymal cells. The specific activity of the important endopeptidase cathepsin D in endothelial and Kupffer cells was about 12 and 36 times higher, respectively, than the activity in parenchymal cells. These results are in agreement with an important role of Kupffer and endothelial cells in the degradation of proteins and protein containing material of exogenous origin.

Aminopeptidases↗
PubMed1976

The fine structure of blood vessels in ethylnitrosourea-induced tumours of the rat nervous system: with special reference to the breakdown of the blood-brain barrier.

The fine structure of capillaries in and around ethylnitrosourea-induced tumours, gliomas and schwannomas, was examined in rats. A great variation was observed in the severity of changes: the degree of abnormality depended on the histological type and size of the tumour and on the site of the capillaries within the neoplasm. Endothelial cells, basement membranes and pericytes all demonstrated changes in their fine structure. The most striking alterations occurred in the endothelial cells: luminal cell membranes, tight junctions and pinocytotic activity were all modified. The widened extracellular spaces, particularly around capillaries, were frequently seen to contain proteinaceous material and haematogenous cells. Invasion of these spaces by neoplastic cells, however, rarely occurred. Formation of new capillaries was indicated by the mitotic activity of endothelial cells. These changes in the blood vessels of cerebral tumours have an important role in the breakdown of the blood-brain barrier.

Animals↗
PubMedDate not supplied

The effects of pathophysiologic state on the metabolism of vasoactive peptides by mammalian lung.

The pulmonary circulation plays a major role in the metabolism of angiotensin I (AI) and bradykinin through the activity of endothelial cell membrane-bound dipeptidylcarboxypeptidase, converting enzyme of kininase II. This report describes studies which investigate the effects of hypoxia on the function of converting enzyme in vivo in dogs and in endothelial cells in culture. Pulmonary converting enzyme function was assessed by both a blood pressure response technique and radioimmunoassay of bradykinin. Conversion of AI in vivo is decreased during acute alveolar hypoxia. At a PaO2 of 30 mmHg, conversion of AI is decreased to one-half control values. This decrease in AI conversion could not be related to hemodynamic factors in the pulmonary vasculature induced by hypoxia. Clearance of bradykinin by lung converting enzyme decreased from 96% at PaO2 levels above 95 torr to 0% below 26 torr. Hypoxic inhibition of enzyme activity was rapid in onset (less than 2 min), was closely correlated with PaO2 (r = 0.92, p less than 0.001) and reversible within 2 min after return to room air breathing. Converting enzyme activity of the systemic vascular bed also is inhibited by hypoxia. Converting enzyme activity also was studied by adding bradykinin or AI to endothelial cells in culture flasks and measuring residual peptide over time by radioimmunoassay. Hypoxia rapidly (less than 2 min) decreased enzyme activity and room air restored it rapidly. There was no enzyme activity below a PO2 of 30 mmHg. Hypoxia does not affect the activity of purified converting enzyme free of the endothelial cell. Metabolic and respiratory acidosis, as well as metabolic and respiratory alkalosis, had no significant effect on converting enzyme function in vivo in intact animals. While converting enzyme is resistant to a number of pathophysiological insults, it is extraordinarily responsive to acute hypoxia which may have important implications for systemic vasomotor control in conditions associated with clinical hypoxia and hypoxemia.

Acid-Base Equilibrium↗
PubMed2024

SCAR-6 elncRNA locus epigenetically regulates PROZ and modulates coagulation and vascular function.

In this study, we characterize a novel lncRNA-producing gene locus that we name Syntenic Cardiovascular Conserved Region-Associated lncRNA-6 (scar-6) and functionally validate its role in coagulation and cardiovascular function. A 12-bp deletion of the scar-6 locus in zebrafish (scar-6gib007Δ12/Δ12) results in cranial hemorrhage and vascular permeability. Overexpression, knockdown and rescue with the scar-6 lncRNA modulates hemostasis in zebrafish. Molecular investigation reveals that the scar-6 lncRNA acts as an enhancer lncRNA (elncRNA), and controls the expression of prozb, an inhibitor of factor Xa, through an enhancer element in the scar-6 locus. The scar-6 locus suppresses loop formation between prozb and scar-6 sequences, which might be facilitated by the methylation of CpG islands via the prdm14-PRC2 complex whose binding to the locus might be stabilized by the scar-6 elncRNA transcript. Binding of prdm14 to the scar-6 locus is impaired in scar-6gib007Δ12/Δ12 zebrafish. Finally, activation of the PAR2 receptor in scar-6gib007Δ12/Δ12 zebrafish triggers NF-κB-mediated endothelial cell activation, leading to vascular dysfunction and hemorrhage. We present evidence that the scar-6 locus plays a role in regulating the expression of the coagulation cascade gene prozb and maintains vascular homeostasis.

Animals↗
PubMed1978

Changes in the activity of the reticulo-endothelial system of rats during an infection with T. lewisi.

Data presented show that during the course of a Trypanosoma lewisi infection in rats there was both an activation of the phagocytic cells of the liver and spleen and an increase in their numbers. There was a marked lymphoid hyperplasia in the white pulp of the spleen with an increase in the number and size of the lymphoid follicles. Degenerative changes occurred in the liver parenchymal cells during the infection, and at certain stages large numgers of mononuclear cells were observed in the vascular sinusoids and other vessels of the liver.

Animals↗
PubMed1979

Effect of contact inhibition on the regulation of cholesterol metabolism in cultured vascular endothelial cells.

Cholesterol synthesis in actively growing bovine vascular endothelial cells is regulated by low density lipoprotein (LDL) at a step prior to mevalonate formation, in a manner comparable to that found in aortic smooth muscle cells. LDL uptake by these cells is associated with induction of cholesterol esterification, an increase in total cell cholesterol, and an inhibition of endogenous sterol synthesis. In contrast, cholesterol metabolism in confluent contact-inhibited endothelial cultures was not significantly affected by LDL even though the cells bind the lipoprotein at high affinity receptor sites. Lysosomal degradation and subsequent regulatory effects on cellular cholesterol metabolism, however, were observed in contact-inhibited endothelial cells incubated with cationized rather than native LDL. Cationized LDL enter the cells independently of the high affinity sites. Therefore, the primary regulation of cholesterol metabolism in these cells is neither through the appropriate intracellular enzymes nor through the high affinity surface receptors, but via an inhibition of LDL internalization. It is suggested that this inhibition is due to a strict contact-inhibited morphology which enables the endothelium of the larger arteries to function as a selective barrier to the high circulating levels of plasma LDL.

Animals↗
PubMed1978

Dexamethasone inhibition of experimental endothelial cell proliferation in retinal venules.

The observation that endothelial cell proliferation in retinal blood vessels is induced by ocular trauma in rats has been extended to mice. Indomethacin, 10 mg/kg/day, failed to block incorporation of tritiated thymidine into nuclei of venular endothelial cells in rat retinas observed 40 hr after puncturing the lens, but dexamethasone effectively suppressed tritiated thymidine incorporation, with 50% inhibition obtained with 0.2 mg/kg/day. The prostaglandin pathway does not appear essential to the activation of endothelial cell proliferation in this system.

Animals↗