Detection of von Willebrand Factor and Tissue Factor in Platelets-Fibrin Rich Coronary Thrombi in Acute Myocardial Infarction

Yamashita, Atsushi; Sumi, Takahiro; Goto, Shinichi; Hoshiba, Yasunari; Nishihira, Kensaku; Kawamoto, Riichirou; Hatakeyama, Kinta; Date, Hiroyuki; Imamura, Takuroh; Ogawa, Hisao; Asada, Yujiro

doi:10.1016/j.amjcard.2005.07.105

Cited by 51 publications

(36 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In fact, histologic examination of coronary thrombi aspirated from patients with acute myocardial infarction revealed a prominent co-localization of VWF with platelets. 12,13 These observations are in line with animal models showing that ADAMTS13 deficiency exacerbates VWF-dependent thrombus formation on disrupted plaques, thereby impacting also on the resulting infarct size.…”

supporting

confidence: 71%

Acquired intracoronary ADAMTS13 deficiency and VWF retention at sites of critical coronary stenosis in patients with STEMI

Pedrazzini

Biasco

Sulzer

et al. 2016

Blood

View full text Add to dashboard Cite

von Willebrand factor (VWF) mediates platelet adhesion and agglutination at sites of vascular injury. VWF is a large multimeric glycoprotein, which circulates in a coiled, non-adhesive conformation. When exposed to high shear stress, VWF unfolds and elongates to highly adhesive multimer strands that adhere on exposed collagen fibers, and by interacting with platelet glycoprotein Ib-a, recruit platelets to the injury site. 1,2Recent in vivo work showed that transition from laminar to turbulent flow, as observed at sites of stenotic vessels, is the most important trigger for adhesive conformational change of VWF. Additionally, the ability of VWF to tether platelets is directly proportional to its multimeric size. The latter is regulated by ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type-1 repeats, member 13), a metalloprotease that cleaves VWF multimers within the unfolded A2 domain, thereby reducing VWF multimer size, and by this, decreasing VWF adhesiveness. 4 We postulated that transition from laminar to turbulent flow at sites of critical coronary stenosis may cause a local imbalance between VWF and ADAMTS13, 5 which would be responsible for the presence of highly adhesive VWF multimers mediating platelet adhesion and agglutination, and ultimately responsible for acute occlusion. The aim of this investigation was to evaluate systemic and intracoronary thrombin generation, VWF, and ADAMTS13 activity in patients with acute coronary syndromes (ACS) with angiographic evidence of acute thrombotic coronary occlusion.We investigated 27 patients (24 men; median age, 65 years; interquartile range [IQR], 54-74; range, 41-84) undergoing emergency cardiac catheterization for hemodynamically stable ACS presenting with ST-elevation myocardial infarction (STEMI) who gave written informed consent. The culprit lesion was determined angiographically in two orthogonal projections and was defined by the combination of: (1) abrupt (typical) vessel occlusion; and (2) complete absence of (or severely impaired) peripheral coronary flow. Infarct localization was anterior in 9 patients, infero-posterior in 16, and lateral in 2. Maximal creatine kinase value was median 1440 U/L (IQR, 922-2262; range, 750-5800) and the extent of the underlying coronary artery disease assessed by the Syntax score was 17 6 7. All patients underwent percutaneous coronary intervention/stenting with a median time from chest pain to onset-balloon of 105 minutes (IQR, 62-150; range, 20-1140).Blood samples were obtained at 3 different sites before stenting: from the femoral vein and at the ostia of the right or left coronary artery through a coronary guiding 6 French catheter, and 1-3 cm distal to the site of occlusion with a conventional 6 French compatible thrombus aspiration catheter advanced through the lesion. In a preliminary phase, we verified that blood sampling by coronary catheter did not alter results for thrombin-generation markers, VWF, and ADAMTS13 compared with peripheral venipuncture. Additionally, care was taken to perform ...

show abstract

supporting

confidence: 71%

Acquired intracoronary ADAMTS13 deficiency and VWF retention at sites of critical coronary stenosis in patients with STEMI

Pedrazzini

Biasco

Sulzer

et al. 2016

Blood

View full text Add to dashboard Cite

show abstract

“…23 Moreover, VWF and ADAMTS13 were both identified in coronary thrombi isolated from patients with AMI, although UL-VWF has been detected in plasma from patients with AMI. 20,22,[24][25][26] Whereas it is difficult to directly compare the extent of acute injury in our experimental mouse model of AMI with the clinical risk of MI occurrence, these clinical data at least further indicate a role for ADAMTS13 in MI progression. One limitation of clinical case-control studies is the intricacy of determining whether low ADAMTS13 levels are cause or consequence of the cardiovascular event.…”

Section: Discussionmentioning

confidence: 99%

Protective anti-inflammatory effect of ADAMTS13 on myocardial ischemia/reperfusion injury in mice

Meyer

Savchenko

Haas

et al. 2012

Blood

108

128

View full text Add to dashboard Cite

Coronary heart disease is a major cause of death in the western world. Although essential for successful recovery, reperfusion of ischemic myocardium is inevitably associated with reperfusion injury. To investigate a potential protective role of ADAMTS13, a protease cleaving von Willebrand factor multimers, during myocardial ischemia/reperfusion, we used a mouse model of acute myocardial infarction. We found that Adamts13 ؊/؊ mice developed larger myocardial infarctions than wild-type control mice, whereas treatment of wild-type mice with recombinant human ADAMTS13 (rhADAMTS13) led to smaller infarctions. The protective effect of ADAMTS13 was further confirmed by a significant reduction of cardiac troponin-I release and less myocardial apoptosis in mice that received rhADAMTS13 compared with controls. Platelets adherent to the blood vessel wall were observed in few areas in the heart samples from mice treated with vehicle and were not detected in samples from mice treated with rhADAMTS13. However, we observed a 9-fold reduction in number of neutrophils infiltrating ischemic myocardium in mice that were treated with rhADAMTS13, suggesting a potent anti-inflammatory effect of ADAMTS13 during heart injury. Our data show that ADAMTS13 reduces myocardial ischemia/reperfusion injury in mice and indicate that rhADAMTS13 could be of therapeutic value to limit myocardial ischemia/reperfusion injury. (Blood. 2012;120(26):5217-5223) IntroductionCoronary heart disease is the leading cause of death in the western world with approximately 1 million myocardial infarctions (MIs) each year just in the United States. 1,2 Acute myocardial infarction (AMI) is caused by thrombotic occlusion of a coronary artery. Although rapid restoration of the coronary circulation is critical for successful treatment, reperfusion itself exacerbates injury of previously ischemic myocardium. 1 The exact mechanisms of myocardial ischemia/reperfusion (MI/R) injury are not fully understood. 1 Given that cardiac ischemia is either unpredictable (MI) or inevitable (in patients undergoing cardioplegic arrest), there is great interest in developing strategies to minimize injury. von Willebrand factor (VWF) and its cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type-1 motif, member 13) play a pivotal role in platelet adhesion and thrombus formation. By specifically cleaving the VWF A2 domain, ADAMTS13 digests the most thrombogenic ultra-large VWF multimers (UL-VWF) into smaller, less hemostatically active VWF molecules. In addition, ADAMTS13's action on VWF downregulates inflammatory responses. As a result, using experimental mouse models, ADAMTS13 was shown to reduce both thrombosis and inflammation, including atherosclerosis. [3][4][5] An increasing amount of clinical evidence points to the possibility that VWF and ADAMTS13 are involved in MI pathogenesis. 6 To test this experimentally, we used a mouse model of acute myocardial infarction. Using mice deficient in ADAMTS13 and treating wild-type mice with human rhADAM...

show abstract

“…67,68 These studies have elegantly shown the colocalization of VWF with platelet thrombi, tissue factor, and platelets with fibrin in fresh coronary thrombi of patients with MI. Furthermore, shear-induced platelet aggregation and VWF binding to platelets is markedly enhanced in plasma from patients with AMI compared with control plasma.…”

Section: Is Vwf Only a Marker Or Also A Pathogenic Mediator?mentioning

confidence: 99%

“…66 Furthermore, detection of VWF in fresh, human coronary thrombi suggests a causative role of VWF in platelet thrombus growth. 67,68 The distinctive role of VWF is evidenced by elevated VWF levels and VWF activity in the context of ACS. The unweighted meanϮSD of published VWF data 64,69 -82 shows that patients with AMI (196Ϯ39%; nϭ877) have markedly increased VWF values compared with unstable angina pectoris (156Ϯ41%; nϭ345) and CAD (140Ϯ30%; nϭ300) patients, as well as healthy control subjects (110Ϯ17%; nϭ394).…”

Section: Vwf and Acsmentioning

confidence: 99%

Von Willebrand Factor in Cardiovascular Disease

2008

View full text Add to dashboard Cite

Abstract-von Willebrand factor (VWF) plays a pivotal role in platelet adhesion and aggregation at sites of high shear rates (eg, in coronary arteries that have stenotic or ruptured atherosclerotic plaque lesions). Numerous studies have investigated the relationship between VWF plasma levels and thromboembolic cardiovascular events. In contrast to the rather weak association in the general population, in patients with preexisting vascular disease, VWF is significantly predictive for adverse cardiac events, including death. Likewise, VWF typically rises during the course of acute coronary syndrome, and the extent of this VWF release is an independent predictor of adverse clinical outcome in these patients. Key Words: coronary disease Ⅲ myocardial infarction Ⅲ platelets Ⅲ thrombosis Ⅲ von Willebrand factor F or Ͼ150 years, it has been known that alterations in blood flow, vascular wall, and blood components, the so-called Virchow's triad, 1 may progressively lead to thrombus formation. Yet, a more complete understanding of the complex interactions among the vascular endothelium, platelet adhesion, activation, aggregation, and clotting factor activation involved in this process is still emerging from contemporary research.Under physiological conditions, the vascular endothelium produces many substances that contribute importantly to hemostasis, fibrinolysis, and regulation of vessel tone and permeability. One such substance is the multimeric glycoprotein von Willebrand factor (VWF), which is produced almost exclusively by endothelial cells. 2 Plasma levels of VWF are raised in different states of endothelial damage and have therefore been proposed as useful markers of endothelial dysfunction. 3 Along this line, blockade of nitric oxide enhances the stimulated release of VWF in humans. 4,5 Furthermore, VWF plays a crucial role in platelet adhesion and aggregation under high shear conditions. 6 Finally, VWF supports the third component of Virchow's triad, clotting factor activation, by acting as a carrier protein and stabilizer for factor VIII. 7 Almost all acute coronary syndromes (ACS) result from thrombus formation in preexisting coronary atherosclerosis. As a result of plaque rupture and exposure of prothrombotic subendothelial matrix, local thrombus formation occurs, which subsequently leads to coronary artery occlusion and acute myocardial infarction (AMI). The presence of VWF has been shown to play a pivotal role in platelet aggregation at sites of high shear, eg, at the sites of lesions in the coronary arteries. 8 Accordingly, VWF is a well-characterized marker of cardiovascular risk, and VWF plasma levels are increased in patients with ACS. 9 Considering the central role of VWF in thrombogenesis, therapies that specifically inhibit VWF are of particular interest as potential new antiplatelet drugs.

show abstract

Detection of von Willebrand Factor and Tissue Factor in Platelets-Fibrin Rich Coronary Thrombi in Acute Myocardial Infarction

Cited by 51 publications

References 19 publications

Acquired intracoronary ADAMTS13 deficiency and VWF retention at sites of critical coronary stenosis in patients with STEMI

Acquired intracoronary ADAMTS13 deficiency and VWF retention at sites of critical coronary stenosis in patients with STEMI

Protective anti-inflammatory effect of ADAMTS13 on myocardial ischemia/reperfusion injury in mice

Von Willebrand Factor in Cardiovascular Disease

Contact Info

Product

Resources

About