Modulation of the fibrinolytic response of cultured human vascular endothelium by extracellularly generated oxygen radicals.

We investigated whether oxygen radicals generated during ischemia-reperfusion trigger postischemic inflammation in the heart. Closed-chest dogs underwent 90-min coronary artery occlusion, followed by 1- or 3-h reperfusion: 10 dogs received the cell-permeant oxygen radical scavenger N-(2-mercaptopropionyl)-glycine (MPG; 8 mg · kg−1 · h−1intracoronary) beginning 5 min before reperfusion, and 9 dogs received vehicle. Blood flow (microspheres), intercellular adhesion molecule (ICAM)-1 protein expression (immunohistochemistry), ICAM-1 gene activation (Northern blotting), nuclear DNA binding activity of nuclear factor (NF)-κb and AP-1 (electrophoretic mobility shift assays), and neutrophil (PMN) accumulation (myeloperoxidase activity) were assessed in myocardial tissue samples. ICAM-1 protein expression was high in vascular endothelium after ischemia-reperfusion but was markedly reduced by MPG. MPG treatment also markedly decreased expression of ICAM-1 mRNA and tissue PMN accumulation. Nuclear DNA binding activities of NF-κB and AP-1, increased by ischemia-reperfusion, were both markedly decreased by MPG at 1 h of reperfusion. However, by 3 h, AP-1 activity was only modestly reduced by MPG and NF-κB activity was not significantly different from ischemic-reperfused controls. These results suggest that oxygen radicals generated in vivo during reperfusion trigger early activation of NF-κb and AP-1, resulting in upregulation of the ICAM-1 gene in vascular endothelium and subsequent tissue accumulation of activated PMNs.

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Oxygen radicals participate in alloxan-induced pulmonary EDEMA

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100159047 ◽

1990 ◽

Vol 48 (3) ◽

pp. 298-299

Author(s):

Tomoo Kawada ◽

Michio Arakawa ◽

Kenjiro Kambara ◽

Takashi Segawa ◽

Fumio Ando ◽

...

Keyword(s):

Pulmonary Edema ◽

Oxygen Radicals ◽

Bolus Injection ◽

Physiological Saline ◽

Baseline Period ◽

Alveolar Epithelial Cells ◽

Control Group ◽

Intervention Period ◽

Lung Water ◽

Electron Microscopic

We know that alloxan causes increased-permeability pulmonary edema and that alloxan generates oxygen radicals (H2O2, O2−, ·OH) in blood. Therefore, we hypothesize that alloxan-generated oxygen radicals damage pulmonary capillary endothelial cells, and, possibly, alveolar epithelial cells as well. We examined whether oxygen radical scavengers, such as catalase or dimethylsulfoxide (DMSO), protected against alloxaninduced pulmonary edema.Five dogs in each following group were anesthetized: control group: physiological saline (20ml/kg/h); alloxan group: physiological saline + alloxan (75mg/kg) bolus injection at the beginning of the experiment; catalase group: physiological saline + catalase (150,000u/kg) bolus injection before injection of alloxan; DMSO group: physiological saline + DMSO (0.4mg/kg) bolus injection before alloxan. All dogs had 30-min baseline period and 3-h intervention period. Hemodynamics and circulating substances were measured at the specific points of time. At the end of intervention period, the dogs were killed and had the lungs removed for electron microscopic study and lung water measurement with direct destructive method.

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Post-stroke neurogenesis and the neurovascular niche: Newly born neuroblasts localize to peri-infarct cortex in close association with the vascular endothelium

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9591524.0214 ◽

2005 ◽

Vol 25 (1_suppl) ◽

pp. S214-S214 ◽

Cited By ~ 3

Author(s):

S Thomas Carmichael ◽

John Ohab ◽

Jimmy Nguyen

Keyword(s):

Vascular Endothelium ◽

Close Association ◽

Post Stroke ◽

Neurovascular Niche

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Polyphenolic compounds from Clusiaceae plants modulating angiogenesis and vascular endothelium

Planta Medica ◽

10.1055/s-0031-1282140 ◽

2011 ◽

Vol 77 (12) ◽

Author(s):

A Lavaud ◽

R Soletti ◽

P Richomme ◽

R Andriantsitohaina ◽

D Guilet

Keyword(s):

Vascular Endothelium ◽

Polyphenolic Compounds

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Ultrastructural Changes of the Tissue Thromboplastin after Intravenous Injection in Rabbits

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646670 ◽

1978 ◽

Vol 39 (01) ◽

pp. 201-209 ◽

Cited By ~ 1

Author(s):

Hiroshi Hasegawa ◽

Hiroshi Nagata ◽

Makoto Murao

Keyword(s):

Intravenous Injection ◽

Vascular Endothelium ◽

Model Experiment ◽

Venous Return ◽

Ultrastructural Changes ◽

Membrane Structures ◽

Tissue Thromboplastin ◽

Short Time ◽

Sheet Membrane

SummaryAttempts were made to demonstrate ultrastructural changes of the tissue thromboplastin after intravenous injection, as a model experiment on the pulmonary microthrombi formation induced by the tissue thromboplastin circulating from venous return.Concentrically arranged membrane structures of the injected thromboplastin disappeared in extremely short time after the injection of the thromboplastin in rabbits. The long sheet membrane of the injected thromboplastin was frequently seen as adhered to the vascular endothelium or to the surface of blood corpuscles. Furthermore, fibrin fibres were formed in contact with the long sheet membrane of the thromboplastin. Membrane structures were not found anywhere in the control rabbits.

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Elevated Fibronectin Plasma Levels in Diabetes Mellitus Are Expression of Increased Synthesis and Release by Vascular Endothelium

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646547 ◽

1989 ◽

Vol 61 (01) ◽

pp. 150-151 ◽

Cited By ~ 3

Author(s):

R Musso ◽

A Longo ◽

R R Cacciola ◽

A Lombardo ◽

R Giustolisi ◽

...

Keyword(s):

Diabetes Mellitus ◽

Vascular Endothelium ◽

Plasma Levels

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The Use of Desmopressin Acetate (DDAVP) as a Test of the Fibrinolytic Capacity of Patients – Analysis of Responders and Non-Responders

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657246 ◽

1982 ◽

Vol 48 (02) ◽

pp. 156-161 ◽

Cited By ~ 36

Author(s):

E J P Brommer ◽

M M Barrett-Bergshoeff ◽

R A Allen ◽

I Schicht ◽

R M Bertina ◽

...

Keyword(s):

Renal Insufficiency ◽

Plasminogen Activator ◽

Vascular Endothelium ◽

Fibrinolytic Activity ◽

Baseline Level ◽

Poor Response ◽

Facial Flushing ◽

Spontaneous Thrombosis ◽

Type Iv ◽

Fibrinolytic Capacity

SummaryIntravenous infusion of desmopressin (DDAVP, 0.4 μg/kg b.w. in 12’) causes an increase in the level of extrinsic plasminogen activator, measured in plasma euglobulin fractions with added C1-inactivator on fibrin plates. A poor response or no response at all was elicited in two out of 21 patients with spontaneous thrombosis, 18/38 with hyperlipoproteinaemia and 10/14 with terminal renal insufficiency requiring haemodialysis.Haemodilution during the first 30’ after starting the DDAVP-infusion occurred both in responders and in non-responders; so did haemodynamic reactions: increase in heart rate, drop in diastolic blood pressure, facial flushing. The rise of fibrinolytic activity was shown not to be associated with decreased hepatic blood flow. Normal factor VIII-rises in “non-responders” indicate the responsiveness of the receptive organs, including the hypothalamus, to DDAVP.Despite a normal baseline level of fibrinolytic activity in the blood, as occurs for instance in terminal renal insufficiency, the vascular endothelium may be refractory to stimulation. In some patients, especially in type IV hyperlipoproteinaemia, a selective defect of the release of plasminogen activator is postulated. In subjects with low fibrinolytic activity at rest, as observed in spontaneous thromboembolism and in hypertriglyceridaemia, the failure to release plasminogen activator upon stimulation with DDAVP might be a consequence of an impairment of synthesis as well.

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