Endothelial dysfunction and systemic inflammation in persons with echolucent carotid plaques

2006 ◽  
Vol 96 (07) ◽  
pp. 53-59 ◽  
Author(s):  
Ellisiv Mathiesen ◽  
Jean Amiral ◽  
Anne Vissac ◽  
John-Bjarne Hansen ◽  
Ann-Trude Notø
Keyword(s):  
Endothelial Dysfunction ◽  
Carotid Stenosis ◽  
Plasminogen Activator ◽  
Systemic Inflammation ◽  
Plasminogen Activator Inhibitor ◽  
Plaque Morphology ◽  
Carotid Plaques ◽  
Pulsed Wave Doppler ◽  
Hs Crp ◽  
Von Willebrand

SummaryEcholucent carotid plaques are associated with high risk for future ischemic cerebrovascular events independent of the degree of stenosis. Elevated levels of markers of systemic inflammation and endothelial dysfunction are predictors for future myocardial infarction and stroke.The present study was undertaken to investigate the relations between plaque morphology, endothelial dysfunction assessed by tissue-plasminogen activator antigen (t-PA ag) and von Willebrand factor (vWF), and systemic inflammation in persons with carotid stenosis.We conducteda crosssectional study including 133 persons with carotid stenosis and 138 controls without stenosis recruited from the populationbased Tromsø Study. High-resolution B-mode and colour Doppler/pulsed-wave Doppler ultrasonography of both carotid arteries was performed, and plaque morphology in terms of echogenicity was assessed. Persons with carotid stenosis had significantly higher plasma t-PA and vWF concentrations than controls. There was a significant inverse relationship between t-PA ag and plaque echogenicity (p=0.034).The increased plasma t-PA ag in persons with carotid stenosis was not associated with increased plasminogen activator inhibitor-I (PAI-1).Persons with echolucent carotid plaques had higher degree of systemic inflammation, and plasma t-PA and vWF concentration increased significantly across quartiles of WBC, fibrinogen, and hs-CRP. Our findings may suggest that plasma t-PA may be superior to vWF asa marker for endothelial dysfunction due to its ability to discriminate between various plaque echogenicity, and that the predictive role of t-PA ag in cardiovascular disease is independent of inhibited fibrinolysis.

scholarly journals State-of-the-Art Review: Endothelial Dysfunction in the Pathogenesis of Atherosclerosis

2001 ◽  
Vol 7 (4) ◽  
pp. 276-280 ◽  
Author(s):  
Pavel Poredoš
Keyword(s):  
Risk Factors ◽  
Endothelial Dysfunction ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Common Denominator ◽  
Atherosclerotic Lesions ◽  
Circulating Markers ◽  
Thrombotic Complications ◽  
Atherosclerotic Process ◽  
Von Willebrand

Healthy endothelium plays a central role in cardiovascular control. Therefore, endothelial dysfunction (ED), which is characterized by an imbalance between relaxing and contracting factors, procoagulant and anticoagulant substances, and between proinflammatory and antiinflammatory mediators, may play a particularly significant role in the pathogenesis of atherosclerosis. Endothelial dysfunction is closely related to different risk factors of atherosclerosis, and to their intensity and duration. The involvement of risk factors in ED is also supported by results of interventions studies that showed regression of ED with treatment of risk factors. Because risk factors are commonly accompanied by decreased bioavailability of nitric oxide, the common denominator whereby different risk factors cause ED is most probably increased oxidative stress. Endothelial dysfunction may promote atherogenesis through different mechanisms such as increased adherence of monocytes, macrophages, and enhanced permeability of the endothelial layer. Further, ED probably plays an important role in the growth of atherosclerotic lesions and in the development of thrombotic complications in late stages of the disease. Because ED is a key underlying factor in the atherosclerotic process, markers of endothelial abnormalities have been sought. Detection of ED is based on tests of endothelium-dependent vasomotion (dilation capability of peripheral and coronary arteries) and on circulating markers of endothelial function (endothelin-1, von Willebrand factor, tissue plasminogen activator, plasminogen activator inhibitor, and adhesion molecules). Using these tests it is possible to follow the dose response of harmful effects of risk factors, and the effects of preventive procedures on vessel wall function.

Coagulation and Fibrinolytic Activity in Behçet's Disease

1991 ◽  
Vol 66 (03) ◽  
pp. 292-294 ◽  
Author(s):  
K K Hampton ◽  
M A Chamberlain ◽  
D K Menon ◽  
J A Davies
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Behçet’S Disease ◽  
Fibrinolytic Activity ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Plasminogen Activator Inhibitor ◽  
Behcet's Disease ◽  
Tissue Plasminogen ◽  
Von Willebrand

SummaryCoagulation and fibrinolytic activities were studied in 18 subjects with Behçet's disease and compared with results from 14 matched control patients suffering from sero-negative arthritis. Significantly higher plasma concentrations (median and range) were found in Behçet's patients for the following variables: fibrinogen 3.7 (1.7-6.9) vs 3.0 (2.0-5.1) g/1, p <0.05; von Willebrand factor antigen, 115 (72-344) vs 74 (60-119)%, p <0.002; plasminogen activator activity (106/ECLT2) 219 (94-329) vs 137 (78-197) units, p <0.002; tissue plasminogen activator inhibitor (t-PA-I) activity, 9.1 (5.5-19.3) vs 5.1 (1.8-12.0) IU/ml, p <0.002; and PAI-1 antigen, 13.9 (4.5-20.9) vs 6.4 (2.4-11.1) ng/ml, p <0.002. Protein C antigen was significantly lower: 97 (70-183) vs 126 (96-220)%, p <0.02. No differences were observed in antithrombin III activity or antigen, factor VIII coagulant activity, fibrinopeptides A and Bβ15-42, plasminogen, α-2-antiplasmin, functional and immunological tissue-plasminogen activator, thrombin-antithrombin complexes and D-dimer. Levels of tissue plasminogen activator inhibitor (activity and antigen) correlated with disease activity while fibrinogen and von Willebrand factor concentrations did not. Seven of the 18 subjects with Behçet's disease had suffered thrombotic events but it was not possible to distinguish these from the 11 patients without thrombosis using the assays performed. The results suggest the abnormal fibrinolytic activity in Behçet's disease is due to increased inhibition of tissue plasminogen activator. No abnormality of coagulation or fibrinolytic activity specific to Behçet's disease was detected.

scholarly journals Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways

Blood ◽  
1990 ◽  
Vol 76 (12) ◽  
pp. 2520-2526 ◽  
Author(s):  
SJ van Deventer ◽  
HR Buller ◽  
JW ten Cate ◽  
LA Aarden ◽  
CE Hack ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Plasminogen Activator ◽  
Cell Activation ◽  
Plasminogen Activator Inhibitor ◽  
Contact System ◽  
Initial Increase ◽  
Cytokine Release ◽  
Endothelial Cell Activation ◽  
System A ◽  
Von Willebrand

Abstract Endotoxemia was evoked by bolus injection of Escherichia coli endotoxin (2 ng/kg body weight) in six healthy subjects to investigate the early kinetics of cytokine release in relation to the development of clinical and hematologic abnormalities frequently seen in gram-negative septicemia. The plasma concentration of tumor necrosis factor (TNF) increased markedly after 30 to 45 minutes, and reached a maximal level after 60 to 90 minutes. In each volunteer, the initial increase of plasma interleukin 6 (IL-6) concentrations occurred 15 minutes after the initial TNF increase, and maximal IL-6 concentrations were reached at 120 to 150 minutes. A transient increase in body temperature and pulse rate occurred simultaneously with the initial TNF and IL-6 increases, whereas a significant decrease in blood pressure occurred after 120 minutes. These changes were proportional to the changes in TNF and IL-6 concentrations. Coagulation activation, as assessed by a rise of prothrombin fragments and thrombin-antithrombin III complexes, was noted after 120 minutes, in the absence of activation of the contact system. A two- to sixfold increase in the concentrations of tissue plasminogen activator (t-PA) and von Willebrand factor antigen indicated endothelial cell activation. This increase started at 120 and 90 minutes, respectively. The release of t-PA coincided with activation of the fibrinolytic pathway, as measured by plasmin-alpha 2-antiplasmin complexes. The fibrinolytic activity of t-PA was subsequently offset by release of plasminogen activator inhibitor, observed 150 minutes after the endotoxin injection, and reaching a peak at 240 minutes. No complement activation was detected. These results show that in humans endotoxin induces an early, rapidly counteracted fibrinolytic response, and a more long-lasting activation of thrombin by a mechanism other than contact system activation. In addition, our data suggest that endotoxin-induced leukopenia and endothelial cell activation are mediated by TNF.

Coagulation and endothelial dysfunction during longterm hyperdynamic porcine bacteremia – effects of selective inducible nitric oxide synthase inhibition

2007 ◽  
Vol 97 (02) ◽  
pp. 304-309 ◽  
Author(s):  
Ales Krouzecky ◽  
Jaroslav Radej ◽  
Richard Rokyta ◽  
Hana Kralova ◽  
Peter Radermacher ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Platelet Count ◽  
Endothelial Dysfunction ◽  
Continuous Infusion ◽  
Plasminogen Activator ◽  
Nitrosative Stress ◽  
Vascular System ◽  
Plasminogen Activator Inhibitor ◽  
Inos Inhibition ◽  
Pai 1

SummaryCoagulation abnormalities have been implicated in the pathogenesis of sepsis and organ dysfunction. Nitric oxide (NO) is regarded as a critical mediator of many vascular pathologies, including sepsis. However, limited evidence is available to document a relationship between NO generated by inducible NO synthase (iNOS) and hemostatic abnormalities in sepsis. Therefore, we evaluated the effects of selective iNOS inhibition on markers of endothelial and coagulation homeostasis in a clinically relevant model of porcine bacteremia induced and maintained for 24 hours (h) with a continuous infusion of live P. aeruginosa. After 12 h of sepsis, animals received either vehicle (Control, n = 7) or continuous infusion of selective iNOS inhibitor L-NIL (n=7). Before as well as 12, 18 and 24 h after starting P. aeruginosafollowing variables related to i) endothelial dysfunction (von Willebrand factor [vWf]; tissue plasminogen activator activity [t-PA]; ii) coagulation (thrombin-antithrombin complexes [TAT]; platelet count); iii) fibrinolysis (t-PA activity, activity of plasminogen activator inhibitor type 1 (PAI-1 act); and iv) oxidative/ nitrosative stress (isoprostanes, nitrate/nitrite levels) were measured. L-NIL inhibited sepsis-induced increase in plasma nitrate/nitrite and isoprostanes concentrations, prevented hypotension and acidosis. L-NIL significantly attenuated sepsisinduced rise in plasma vWF and TAT. P. aeruginosa-induced drop in t-PA activity was blunted by iNOS inhibition, while increased PAI-1 and reduced platelet count were not reversed by the treatment. In conclusion, selective iNOS inhibition was associated with attenuation of sepsis-induced coagulation and endothelial dysfunction suggesting the interplay between mediators of vascular system and hemostatic balance. Reduction of oxidative stress probably contributes to the beneficial effects afforded by iNOS blockade.

Increased thrombin generation in persons with echogenic carotid plaques

2008 ◽  
Vol 99 (03) ◽  
pp. 602-608 ◽  
Author(s):  
Ellisiv Mathiesen ◽  
Bjarne Østerud ◽  
Jean Amiral ◽  
Anne Vissac ◽  
John-Bjarne Hansen ◽  
...  
Keyword(s):  
Carotid Stenosis ◽  
Health Survey ◽  
Thrombin Generation ◽  
Plaque Morphology ◽  
Atherosclerotic Plaques ◽  
Blood Samples ◽  
Carotid Plaques ◽  
Prothrombin Fragment ◽  
Cerebrovascular Events ◽  
Diameter Reduction

SummaryEcholucent carotid plaques are associated with higher risk for future ischemic cerebrovascular events (CVE) than echogenic plaques independent of the degree of stenosis.Elevated markers of thrombin generation are associated with atherosclerotic plaques and are increased in the acute and chronic phases of CVE. The present study was conducted to investigate the influence of plaque morphology on thrombin generation in persons with carotid stenosis. One hundred twenty-eight persons with carotid stenosis (≥35% lumen diameter reduction) and 136 matched controls without stenosis were recruited from the health survey of the Tromsø Study. Blood samples were collected and plaque morphology determined by ultrasonography. Thrombin generation was assessed by thrombin-antithrombin complexes (TAT) and by prothrombin fragment 1+2 (F1+2).Persons with echogenic plaques (n=63) had significantly higher levels of TAT (5.24 μg/l, 4.33–6.14) (mean, 95%CI) than persons with echolucent plaques (n=65) (3.44 μg/l, 2.91–3.96, p<0.001) and controls (n=136) (3.33 μg/l, 3.06–3.60, p<0.001).They also had significantly higher levels of F1+2 (2.14 nM, 1.83–2.45) than persons with echolucent plaques (1.54 nM, 1.38–1.71, p<0.001) and controls (1.49 nM, 1.40–1.58, p<0.001). TAT and F1+2 increased linearly with plaque echogenicity (p=0.002 and p=0.001, respectively) independent of the degree of stenosis. Increased thrombin generation was associated with a significant increase in plasma factorV levels among persons with echogenic plaques compared to echolucent plaques (p=0.049) and controls (p=0.025). The present findings indicate that increasing plaque echogenicity, rather than plaque echolucency and the degree of stenosis, is associated with thrombin generation in persons with carotid stenosis.

scholarly journals Continuous Active State of Coagulation System in Patients With Nonthrombotic Inflammatory Bowel Disease

2011 ◽  
Vol 17 (6) ◽  
pp. 600-604 ◽  
Author(s):  
Huseyin Alkim ◽  
Selime Ayaz ◽  
Canan Alkim ◽  
Aysel Ulker ◽  
Burhan Sahin
Keyword(s):  
Plasminogen Activator ◽  
Degradation Products ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Plasminogen Activator Inhibitor 1 ◽  
Inflammatory Bowel ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Activator Inhibitor ◽  
D Dimer

This study was planned for searching possible changes of the total coagulation and fibrinolysis system in inflammatory bowel disease (IBD) in order to obtain some clues for explaining the relation between IBD and hypercoagulability. A total of 24 patients with ulcerative colitis, 12 patients with Crohn disease, and 20 healthy controls were studied. Platelets; prothrombin time (PT); partial thromboplastin time (PTT); fibrinogen; d-dimer; fibrinogen degradation products; protein C; protein S; antithrombin; thrombin time; von Willebrand factor; coagulation factors V, VII, VIII, IX, XI, and XIII; plasminogen; antiplasmin; tissue plasminogen activator; plasminogen activator inhibitor 1; and prothrombin fragments 1 + 2 were studied. Most of the procoagulants (platelets, fibrinogen, von Willebrand factor, coagulation factor IX, and plasminogen activator inhibitor 1) were found increased together with decreases in some anticoagulants (protein S and antithrombin) in IBD. Also the activation markers of coagulation (d-dimer, fibrinogen degradation products, and prothrombin fragments 1 + 2) were all increased. The parameters of the total coagulation–fibrinolysis system were increased in IBD, regardless of the form and the activity of the disease.

Coagulation and fibrinolytic systems in type I diabetes: effects of venous occlusion and insulin-induced hypoglycaemia

1993 ◽  
Vol 84 (1) ◽  
pp. 79-86 ◽  
Author(s):  
Iwona Wieczorek ◽  
Alistair C. H. Pell ◽  
Brian McIver ◽  
Ian R. MacGregor ◽  
Christopher A. Ludlam ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Venous Occlusion ◽  
Antigen Level ◽  
Tissue Plasminogen ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Von Willebrand

1. The effects of venous occlusion on the coagulation and fibrinolytic systems were investigated in six patients with type 1 (insulin-dependent) diabetes and 11 age- and sex-matched non-diabetic control subjects. The coagulation parameters (fibrinogen, prothrombin time, partial thromboplastin time with kaolin, von Willebrand factor antigen) did not differ between patients and control subjects either before or after 20 min of venous occlusion. No rise was observed in von Willebrand factor antigen after venous occlusion in either group. 2. In the diabetic patients, chronic activation of the fibrinolytic system was found at baseline, which was indicated by a shortened euglobulin lysis time (P < 0.01), increased tissue plasminogen activator activity (P < 0.05) and decreased plasminogen activator inhibitor type 1 antigen level (P < 0.05), when compared with control subjects. In both groups venous occlusion resulted in significant increments in all measurements, except plasminogen activator inhibitor type 1 antigen level. The post-occlusion values did not differ between the two groups, except the plasminogen activator inhibitor type 1 antigen level, which remained significantly lower in the diabetic patients. The mean increments in each parameter did not differ between the two groups. 3. Coagulation and fibrinolysis were assessed in response to acute insulin-induced hypoglycaemia. Von Willebrand factor antigen levels increased significantly in both groups, with no difference in maximal increments. Significant activation of the fibrinolytic system occurred in response to hypoglycaemia, demonstrated by shortened euglobulin lysis time and increased fibrin plate lysis, tissue plasminogen activator antigen level and tissue plasminogen activator activity. The absolute increments were significantly lower in the diabetic group, with an attenuated response of euglobulin lysis time (P < 0.05), tissue plasminogen activator antigen level (P < 0.01) and tissue plasminogen activator activity. 4. Although fibrinolysis was higher in the basal state in the diabetic patients, the attenuated response to hypoglycaemia may indicate the presence of an underlying acquired dysfunction of the vascular endothelium in diabetes. This may be of relevance to the pathogenesis of microvascular disease in type 1 diabetes.

scholarly journals The role of hypercoagulability in the development of osteonecrosis of the femoral head

2012 ◽  
Vol 4 (2) ◽  
pp. 17 ◽  
Author(s):  
Marios G. Lykissas ◽  
Ioannis P. Kostas-Agnantis ◽  
Ioannis D. Gelalis ◽  
Georgios Vozonelos ◽  
Anastasios V. Korompilias
Keyword(s):  
Plasminogen Activator ◽  
Lupus Erythematosus ◽  
Protein C ◽  
Activated Protein C ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Intravascular Coagulation ◽  
S Deficiency ◽  
Increased Risk ◽  
Von Willebrand

Despite the large number of the outstanding researches, pathogenesis of osteonecrosis remains unknown. During the last decades the hypothesis that increased intravascular coagulation may be the pathogenetic mechanism which leads to osteonecrosis is gaining constantly support. Both primary factors of hypercoagulability, such as resistance to activated protein C, protein C and protein S deficiency, low levels of tissue plasminogen activator, high levels of plasminogen activator inhibitor, von Willebrand factor, lipoprotein (a), and secondary factors of hypercoagulability with factors potentially activating intravascular coagulation, such as pregnancy, antiphospholipid antibodies, systemic lupus erythematosus, hemoglobinopathies and sickle cell disease, and hemato-oncologic diseases are discussed in this article. Although coagulation abnormalities in patients with hip osteonecrosis might represent increased risk factors for the development of bone necrosis by predisposing the patient to thromboembolic phenomena, further investigation is needed to indicate the definite correlation between factors leading to increased intravascular coagulation and pathogenesis of osteonecrosis.

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