Tissue factor expression in atrial endothelia associated with nonvalvular atrial fibrillation: possible involvement in intracardiac thrombogenesis

Nakamura, Yoichi; Nakamura, Kazufumi; Fukushima‐Kusano, Kengo; Ohta, Keiko; Matsubara, Hiromi; Hamuro, Tsutomu; Yutani, Chikao; Ohe, Tohru

doi:10.1016/s0049-3848(03)00405-5

Cited by 163 publications

(104 citation statements)

References 37 publications

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“…Several pieces of evidence also indicate that inflammation could have a causal role in the initiation and perpetuation of AF, possibly by inducing structural remodeling of the atrium. This hypothesis is partly based on histological studies which demonstrated inflammatory infiltrates in AF patients and in animal models of AF (34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

Inflammation-sensitive proteins and risk of atrial fibrillation: a population-based cohort study

et al. 2011

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Low-grade inflammation has been repeatedly associated with cardiovascular diseases but the relationship with incidence of atrial fibrillation (AF) remains unclear. We explored the association between elevated plasma levels of inflammation-sensitive proteins (ISPs) and incidence of AF in a population-based cohort.Plasma levels of five ISPs (fibrinogen, haptoglobin, ceruloplasmin, α 1 -antitrypsin and orosomucoid) and two complement factors (C3 and C4) were measured in 6031 men (mean age 46.8 years) without history of myocardial infarction, heart failure, stroke or cancer.Incidence of hospitalizations due to AF during a mean follow-up of 25 years was studied both in relation to individual inflammatory proteins and the number of elevated ISPs.During follow-up, 667 patients were hospitalized with a diagnosis of AF. After adjustment for potential confounding factors, the hazard ratios (HR) for AF were 1.00 (reference), 1.08 (95% CI: 0.88-1.31), 1.07 (CI: 0.84-1.36), and 1.40 (CI: 1.12-1.74), respectively, in men with none, one, two and three or more ISPs in the 4th quartile (p for trend = 0.007). Ceruloplasmin was the only individual ISP significantly associated with incidence of AF after adjustment for confounding factors (HR 1.17 per standard deviation, 95% CI: 1.08-1.26).In conclusion, a score of five ISPs was associated with long-term incidence of hospitalizations due to AF in middle-aged men. Of the individual ISPs, a significant association was observed for ceruloplasmin, a protein previously associated with copper metabolism and oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Inflammation-sensitive proteins and risk of atrial fibrillation: a population-based cohort study

et al. 2011

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“…31 vWf was significantly increased in the injured atrial endothelium containing inflammatory cells in patients with AF who have a history of cardiogenic thromboembolism. 32 From these reports, vWf might be a key factor of LA thrombosis in SPORTS rats. Several recent reports have demonstrated that AF, per se, causes atrial endocardial dysfunction, which is manifested by increased plasminogen activator inhibitor-1 expression, decreased expression of eNOS, tissue factor pathway inhibitor, and thrombomodulin in the LA endocardium, leading to local coagulation imbalance on the internal surface of the atrium.…”

Section: L-arginine Treatment Increased No Production and Decreased Tmentioning

confidence: 96%

Enhancement of Endothelial Function Inhibits Left Atrial Thrombi Development in an Animal Model of Spontaneous Left Atrial Thrombosis

Mawatari

Yoshioka

Toda

et al. 2014

Circ J

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“…31 Since then, many investigators have begun to pay attention to the function of the atrial endocardial cells, a barrier between the blood and atrial cardiomyocytes. [32][33][34][35][36][37] Cai et al demonstrated that AF decreased nitric oxide synthase expression and increased PAI-1 expression in the atrial endocardium of pigs. 32 My group have also shown that AF decreases the mRNA and protein expressions of TFPI and TM in rats.…”

Section: Endocardial Dysfunction Of the Atria In Afmentioning

confidence: 99%

“…34 Several investigators have shown evidence that endocardial function is also impaired in human AF. [35][36][37] Fukuchi et al reported that von Willebrand factor is present on the surface of the atrial endocardium in AF patients. 35 Other investigators have demonstrated the expression of tissue factor in specimens from the atrium of AF patients undergoing valvular surgery.…”

Section: Endocardial Dysfunction Of the Atria In Afmentioning

confidence: 99%

“…35 Other investigators have demonstrated the expression of tissue factor in specimens from the atrium of AF patients undergoing valvular surgery. 37 Taken together, it seems reasonable to speculate that the antithrombotic functions of the atrial endocardium are damaged by AF itself. The processes underlying this impairment of the antithrombotic function of the atrial endocardium will be the future target of investigation.…”

Section: Endocardial Dysfunction Of the Atria In Afmentioning

confidence: 99%

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Molecular Basis of Thromboembolism in Association With Atrial Fibrillation

Yamashita

2007

Circ J

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trial fibrillation (AF), the most common type of arrhythmia in adults, is associated with a 5-fold increase in the incidence of ischemic stroke. 1,2 Stroke in AF patients is believed to be mostly cardioembolic, caused by embolism of left atrial (LA) thrombi, 3 and is an important cause of hospitalizations and cardiovascular deaths, 4 which simultaneously increases the public health cost of managing AF. A recent report revealed that the medical cost of AF was approximately 1% of the total and mainly resulted from the treatment of cerebrovascular events associated with AF. 5 Also, recent clinical trials, including the AFFIRM study, 6 could not demonstrate any differences between rhythm and rate control strategies for AF on patient outcomes, implying that the prevention of stroke by anticoagulation therapy is mandatory and the first step for decreasing the cardiovascular events in these patients. Therefore, total management of AF, complications rather than AF per se, is required.Although it has been quite naturally believed that AF induces thrombus formation in the LA most easily by decreasing the blood flow in the atrium, this is not the case, as many previous studies have demonstrated that not all AF patients are at a high risk of stroke. 7 The presence of LA thrombus in AF patients is only one of the results of AF, and many unidentified processes would be operating under thrombus formation in association with AF before the unfortunate event. Actually, it has not been observed in clinical patients how thrombus gradually forms in the fibrillating atria and also how the thrombus separates from the endocardium, leading to systemic thromboembolism. Therefore, suggesting that thromboembolism in AF patients is caused solely by decreased blood flow may be too simplistic. Rather, it should be noted that many processes exist under the thrombus formation in fibrillating atria and that they have remained unclear for a long time.Over 150 years ago, Virchow postulated that 3 factors predispose to thrombus formation in venous thrombosis: abnormalities in blood flow, blood constituents and the vessel wall. 8 His concept has been believed to be true for more than 100 years and also applied to arterial thrombosis. Thrombus formation in the fibrillating LA has more similarities to thrombosis in the vein than in the artery, because it occurs when blood flow is restricted. Therefore, it would be appropriate to consider the processes of thrombus formation in the atrium in view of Virchow's triad. In the fibrillating atria, the triad corresponds to a decrease in blood flow, abnormalities in coagulation, and atrial endocardial dysfunction. Although these components are invariably and mutually associated with each other, the basic information regarding each component would bring insights into the pathophysiology of AF-associated thrombosis, as well as helping to identify potential therapeutic strategies. Decreased Blood Flow in the Fibrillating AtriumDecreased blood flow in the fibrillating LA is evident in AF patients and has been beli...

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Tissue factor expression in atrial endothelia associated with nonvalvular atrial fibrillation: possible involvement in intracardiac thrombogenesis

Cited by 163 publications

References 37 publications

Inflammation-sensitive proteins and risk of atrial fibrillation: a population-based cohort study

Inflammation-sensitive proteins and risk of atrial fibrillation: a population-based cohort study

Enhancement of Endothelial Function Inhibits Left Atrial Thrombi Development in an Animal Model of Spontaneous Left Atrial Thrombosis

Molecular Basis of Thromboembolism in Association With Atrial Fibrillation

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