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.

The predictive value of markers of fibrinolysis and endothelial dysfunction in the post thrombotic syndrome

2014 ◽  
Vol 111 (06) ◽  
pp. 1031-1040 ◽  
Author(s):  
Anat Rabinovich ◽  
Jacqueline M. Cohen ◽  
Susan R. Kahn
Keyword(s):  
Risk Factors ◽  
Endothelial Dysfunction ◽  
Factor Xiii ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Post Thrombotic Syndrome ◽  
Definition Of ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
D Dimer

SummaryThe post thrombotic syndrome (PTS) develops in 20–40% of deep venous thrombosis (DVT) patients. Risk factors for PTS have not been well elucidated. Identification of risk factors would facilitate individualised risk assessment for PTS. We conducted a systematic review to determine whether biomarkers of fibrinolysis or endothelial dysfunction can predict the risk for PTS among DVT patients. Studies were identified by searching the electronic databases PubMed, EMBASE, Scopus and Web of science. We included studies published between 1990 and 2013, measured biomarker levels in adult DVT patients, and reported rates of PTS development. Fourteen studies were included: 11 investigated the association between D-dimer and PTS; three examined fibrinogen; two measured von Willebrand factor; one measured plasminogen activator inhibitor-1; one assessed ADAMTS-13 (A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats) and one measured factor XIII activity. Studies varied with regards to inclusion criteria, definition of PTS, time point and method of biomarker measurement. We were unable to meta-analyse results due to marked clinical heterogeneity. Descriptively, a significant association with PTS was found for D-dimer in four studies and factor XIII in one study. Further prospective research is needed to elucidate whether these markers might be useful to predict PTS development.

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.

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.

Relation of Urokinase-Type Plasminogen Activator Expression to Presence and Severity of Atherosclerotic Lesions in Human Coronary Arteries

1998 ◽  
Vol 79 (03) ◽  
pp. 579-586 ◽  
Author(s):  
Teresa Padró ◽  
Martin Steins ◽  
Chang-Xun Li ◽  
Kurt Schmid ◽  
Dieter Hammel ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Coronary Arteries ◽  
Plasminogen Activator Inhibitor ◽  
Matrix Remodeling ◽  
Plasminogen Activator Inhibitor 1 ◽  
Atherosclerotic Lesions ◽  
Plaque Disruption ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Tissue Specimens

SummaryUrokinase-type plasminogen activator (UPA) has been implicated in a broad spectrum of pathological processes – e.g. cell adhesion, migration and proliferation and matrix remodeling – that are considered important features of atherogenesis and plaque disruption. In this study, we have analyzed the content and expression of UPA in human coronary arteries and its relation to the presence and severity of atherosclerotic lesions. Segments of coronary arteries obtained from human heart explants (n = 15) were classified by the presence and types of atherosclerotic lesions. UPA was quantitatively determined in protein extracts of the intimal and medial layers. In situ hybridization and immunohistochemical analyses were performed on serial sections of representative tissue specimens. UPA was detected in the extracts as pro-UPA, UPA complexed to plasminogen activator inhibitor-1, or as otherwise inactive UPA antigen, but not in the active two-chain form. Both functional and total UPA were increased several-fold in extracts of advanced lesions, while the ratios of functional over total UPA showed the opposite trend suggesting enhanced UPA inactivation and turnover. UPA expression in early atherosclerotic lesions was particularly prominent in areas of proliferating SMCs in the abluminal part of the neointima, whereas in advanced lesions UPA was widely expressed in macrophage-rich areas adjacent to the rims and shoulder regions of the necrotic cores. The results strongly suggest a causal involvement of UPA in coronary atherogenesis and its clinical outcome.

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.

Endothelial haemostatic factors are associated with progression of urinary albumin excretion in clinically healthy subjects: a 4-year prospective study

1999 ◽  
Vol 97 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Peter CLAUSEN ◽  
Bo FELDT-RASMUSSEN ◽  
Gorm JENSEN ◽  
JanSkov JENSEN
Keyword(s):  
Risk Factors ◽  
Endothelial Dysfunction ◽  
Plasminogen Activator ◽  
Healthy Subjects ◽  
Urinary Albumin Excretion ◽  
Urinary Albumin ◽  
Factor Vii ◽  
Albumin Excretion ◽  
Haemostatic Factors

A slightly elevated urinary albumin excretion rate (UAER), above 5-10 µg/min, is a predictor of atherosclerotic cardiovascular disease. Endothelial dysfunction is an important early feature of atherosclerosis. The plasma concentration of von Willebrand factor (vWF), a potential marker of endothelial dysfunction, predicts a subsequent increase of UAER in patients with diabetes. The aim of this study is to test the hypothesis that high concentrations of vWF as well as other haemostatic factors predict progression of UAER in clinically healthy subjects. UAER was measured together with selected markers of haemostatic function - vWF, tissue plasminogen activator (tPA), plasminogen activator inhibitor, factor VII and fibrinogen - in healthy volunteers aged 40-65 years. After a mean follow-up of 4.1 years, 64 of 74 agreed to a re-examination including re-measurement of UAER. Baseline vWF and tPA were both positively correlated to the change in UAER during follow-up (r = 0.26, P = 0.04 and r = 0.40, P = 0.001 respectively). The mean UAER increased significantly by 7.6 µg/min and 7.5 µg/min respectively in subjects with vWF and tPA above the medians at baseline (P = 0.01 and P = 0.003 respectively), whereas no changes in UAER were seen in subjects with vWF and tPA below the medians. Subjects with high tPA were also characterized by an excess of other cardiovascular risk factors at baseline. No significant differences in these risk factors were present between subjects with high or low vWF. High plasma concentrations of vWF and tPA are associated with progression of UAER in clinically healthy subjects. Both vWF and tPA are secreted by endothelial cells and the results suggest that endothelial dysfunction leads to progression of UAER.

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.

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