fibrin and Atherosclerosis

Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies.. Targeted MR-probes allow the characterization of atherosclerosis on a molecular level. Molecular MRI can identify in vivo markers for the differentiation of stable and unstable plaques. Visualization of early molecular changes has the potential to improve patient-individualized risk-assessment.

Topics: Atherosclerosis; Carotid Arteries; Carotid Artery Diseases; Endothelium, Vascular; Fibrin; Forecasting; Humans; Lipids; Macrophages; Magnetic Resonance Angiography; Molecular Imaging; Molecular Probes; Neovascularization, Pathologic; Peptide Hydrolases; Plaque, Atherosclerotic; Vascular Remodeling

Coagulation factor XII (FXII), formerly known as Hageman factor, is a plasma glycoprotein which exerts a kaleidoscope of biological functions, including the initiation of the intrinsic pathway of blood coagulation, the activation of the kallikrein-kinin system, and the generation of bradykinin and angiotensin. The large body of evidence accumulated over the past decades and the revised cell-based model of hemostasis suggest that FXII may be somehow "redundant" for physiological hemostasis, drawing a potential interpretation of this protein as a possible "innocent" bystander of in vivo hemostasis. Although the contribution of FXII remains unproven in the pathogenesis of venous thromboembolism, perhaps reinforcing this perception of "redundancy," recent work identifies FXII as critical for initiation of thrombosis on artificial surfaces (e.g., polyurethanes or polytetrafluoroethylene catheters), or in patients with strong prothrombotic conditions such as vulnerable atherosclerotic plaques or severe bacterial infections. Important evidence has also emerged from recent investigations using innovative FXII inhibitors in ex vivo animal models, wherein targeted FXII-mediated inhibition of thrombin and fibrin generation may open new avenues for prevention or treatment of certain types of thrombosis. Thus, interest in FXII, waned in the recent past, is again re-emerging, and pointing to important but under-recognized contribution to in vivo hemostasis and thrombosis.

Topics: Animals; Atherosclerosis; Blood Coagulation; Disease Models, Animal; Factor XII; Fibrin; Humans; Thrombin; Thrombosis; Venous Thromboembolism

Accelerated atherosclerosis is the main underlying factor contributing to the high risk of atherothrombotic events in patients with diabetes mellitus and atherothrombotic complications are the main cause of mortality. Like with many bodily systems, pathology is observed when the normal processes are exaggerated or uncontrolled. This applies to the processes of coagulation and thrombosis as well. In diabetes, in fact, the balance between prothrombotic and fibrinolytic factors is impaired and thus the scale is tipped towards a prothrombotic and hypofibrinolytic milieu, which in association with the vascular changes accompanying plaque formation and ruptures, increases the prevalence of ischaemic events such as angina and myocardial infarction. Apart from traditional, modifiable risk factors for cardiovascular disease like hypertension, smoking, elevated cholesterol; rheological properties, endogenous fibrinolysis and impaired platelet activity are rapidly gaining significance in the pathogenesis of atherosclerosis especially in diabetic subjects. Blood clot formation represents the last step in the athero-thrombotic process, and the structure of the fibrin network has a role in determining predisposition to cardiovascular disease. It is no surprise that just like platelets and fibrin networks, erythrocytes have been shown to play a role in coagulation as well. This is in striking contrast to their traditional physiological role of oxygen transport. In fact, emerging evidence suggests that erythrocytes enhance functional coagulation properties and platelet aggregation. Among the spectrum of haematological abnormalities in diabetes, erythrocyte aggregation and decreased deformability of erythrocytes predominate. More importantly, they are implicated in the pathogenesis of microvascular complications of diabetes. The morphology of platelets, fibrin networks and erythrocytes are thus essential role players in unravelling the pathogenesis of cardiovascular complications in diabetic subjects.

Topics: Animals; Atherosclerosis; Blood Coagulation; Blood Platelets; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Erythrocytes; Fibrin; Fibrinolysis; Humans; Plaque, Atherosclerotic; Risk Assessment; Risk Factors; Thrombosis

Although, the first-generation drug eluting stents (DES) have significantly reduced rates of restenosis compared to bare metal stents (BMS), an increased risk of late stent thrombosis (LST) has emerged as a major concern. Pathologic studies of patients dying from late DES thrombosis demonstrates delayed arterial healing characterized by persistent fibrin deposition and poor endothelialization as the primary substrate. However, recent thorough investigations revealed additional mechanisms of stent thrombosis such as hypersensitivity reaction, excessive fibrin deposit with malapposition, or neoatherosclerosis, which are associated with device-specific components and the majority of very late stent thrombosis is likely associated with these abnormal vascular responses. Therefore, although the incidence of stent thrombosis following DES implantation is similar in each period, the underlying mechanisms of this complication may vary. In the current review, the mechanisms of stent thrombosis in the DES era will be discussed using the data from autopsy studies that have been published.

Topics: Adult; Atherosclerosis; Autopsy; Coronary Vessels; Drug-Eluting Stents; Female; Fibrin; Humans; Male; Middle Aged; Myocardial Infarction; Prevalence; Regeneration; Thrombosis; Time Factors

Acquired qualitative abnormalities of fibrinogen molecules, termed acquired dysfibrinogenemia, have been demonstrated in several disease states mostly related to prothrombotic tendency, including multiple myeloma and liver disease. Fibrin is abundant in atherosclerotic plaques. Altered plasma fibrin properties, reflected usually by reduced clot permeability and impaired fibrinolysis, have been reported in patients with acute or prior myocardial infarction, ischemic stroke, and peripheral artery disease. Moreover, prothrombotic clot phenotype has been observed in patients with previous no-reflow phenomenon and stent thrombosis. Growing evidence indicates that acquired dysfibrinogenemia contributes to the progression of atherosclerotic vascular disease and the occurrence of its thrombotic manifestations. The review summarizes current knowledge on the links between fibrin clot phenotype and atherosclerotic vascular disease and describes a wide spectrum of cardiovascular risk factors as modifiers of fibrin network characteristics.

Topics: Atherosclerosis; Fibrin; Fibrinogens, Abnormal; Humans; Plaque, Atherosclerotic; Risk Factors

The formation of blood clots--thrombosis--at sites of atherosclerotic plaque rupture is a major clinical problem despite ongoing improvements in antithrombotic therapy. Progress in identifying the pathogenic mechanisms regulating arterial thrombosis has led to the development of newer therapeutics, and there is general anticipation that these treatments will have greater efficacy and improved safety. However, major advances in this field require the identification of specific risk factors for arterial thrombosis in affected individuals and a rethink of the 'one size fits all' approach to antithrombotic therapy.

Topics: Acute Coronary Syndrome; Animals; Arteries; Atherosclerosis; Blood Platelets; Fibrin; Fibrinolytic Agents; Hemostasis; Humans; Plaque, Atherosclerotic; Thrombin; Thrombosis

Topics: Atherosclerosis; Fibrin; Fibrinogen; Humans

Molecular imaging is a rapidly growing field with the potential to revolutionize cardiovascular medicine by shifting diagnostic focus from functional abnormalities which occur late in a disease process to the biochemical events which precipitate the earliest stages of disease. MRI is a modality well suited to this task as it allows a variety of contrast mechanisms for detection of epitopes of interest, as well as high-resolution anatomical localization and functional information. In this review, we discuss the widerange of available molecular MRI contrast agents and their application to diseases such as atherosclerosis, thrombus imaging, and stem cell tracking, along with opportunities for molecularly targeted drug delivery.

Topics: Animals; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Contrast Media; Fibrin; Humans; Magnetic Resonance Imaging; Nanoparticles; Staining and Labeling; Stem Cells

The goal of molecular imaging is to detect pathologic biomarkers, which can lead to early recognition of diseases, better therapeutic management, and improved monitoring for recurrence. MRI is a particularly attractive method for molecular imaging applications, due to its noninvasive nature, outstanding signal to noise ratio, high spatial resolution, exceptional tissue contrast, and short imaging times. Site-specific MRI contrast agents have been developed to target biologic processes that occur early in the development of atherosclerotic plaques, including angiogenesis and lipid accumulation, or biosignatures that appear later, such as fibrin and tissue factor resulting from plaque rupture. Moreover, targeted contrast agents can also serve as drug delivery vehicles, combining diagnosis and therapy. If ultimately successful, these emerging molecular imaging agents and techniques will allow early disease recognition and quantification prompting therapeutic intervention before serious sequelae ensue.

Topics: Antibiotics, Antineoplastic; Antifibrinolytic Agents; Atherosclerosis; Contrast Media; Doxorubicin; Drug Carriers; Fibrin; Humans; Magnetic Resonance Imaging; Nanostructures; Neovascularization, Pathologic

This review focuses on recent non-invasive or minimally invasive magnetic resonance (MR) approaches to study atherothrombosis. The potential benefits of combining diverse metabolic information obtained by the variety of MR techniques from tissues in vivo and ex vivo and from body fluids in vitro are also briefly discussed. A well established methodology is available for lipoprotein subclass quantification from plasma by 1H MR spectroscopy providing information for assessing the long-term risk of atherosclerosis. Multi-contrast MR imaging in vivo relying on endogenous contrast allows partial characterization of components in atherothrombotic plaques. The use of exogenous contrast agents in MR angiography enhances blood-tissue contrast and provides functional information on plaque metabolism, improving plaque characterization and assessment of plaque vulnerability by MR imaging. Recent applications of molecular targeted MR imaging have revealed novel opportunities for specific early detection of atherothrombotic processes, such as angiogenesis and accumulation of macrophages. Currently, MR imaging and spectroscopy can produce such metabolic in vivo and in vitro information that in combination could facilitate the screening, identification and follow-up of cardiovascularly vulnerable patients in research settings. The recent developments imply that in the near future MR techniques will be part of clinical protocols for individual diagnostics in atherothrombosis.

Topics: Animals; Atherosclerosis; Contrast Media; Ferric Compounds; Fibrin; Fluorocarbons; Humans; Integrin alphaVbeta3; Lipoproteins; Lipoproteins, HDL; Macrophages; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Nanoparticles; Neovascularization, Pathologic; Risk Factors; Thrombosis

Atherothrombosis exposes vascular components to blood. Currently, new antithrombotic therapies are emerging. Herein we investigated thrombogenesis of human arteries with/without atherosclerosis, and the interaction of coagulation and vascular components, we and explored the anti-thrombogenic efficacy of blockade of the P2X purinoceptor 7 (P2X7). A confocal blood flow videomicroscopy system was performed on cryosections of internal mammary artery (IMA) or carotid plaque (CPL) determining/localizing platelets and fibrin. Blood from healthy donors elicited thrombi over arterial layers. Confocal microscopy associated thrombus with tissue presence of collagen type I, laminin, fibrin(ogen) and tissue factor (TF). The addition of antibodies blocking TF (aTF) or factor XI (aFXI) to blood significantly reduced fibrin deposition, variable platelet aggregation and aTF + aFXI almost abolished thrombus formation, showing synergy between coagulation pathways. A scarce effect of aTF over sub-endothelial regions, more abundant in tissue TF and bundles of laminin and collagen type I than deep intima, may suggest tissue thrombogenicity as molecular structure-related. Consistently with TF-related vascular function and expression of P2X7, the sections from CPL but not IMA tissue cultures pre-treated with the P2X7 antagonist A740003 demonstrated poor thrombogenesis in flow experiments. These data hint to local targeting studies on P2X7 modulation for atherothrombosis prevention/therapy.

Topics: Atherosclerosis; Blood Circulation; Blood Coagulation; Blood Platelets; Carotid Arteries; Fibrin; Humans; Microscopy, Confocal; Microscopy, Video; Platelet Aggregation; Receptors, Purinergic P2X7; Thrombosis

Platelet glycoprotein VI (GPVI) acts as a decisive collagen receptor in atherothrombosis. Besides collagen, injured atherosclerotic plaques expose tissue factor (TF) that triggers fibrin formation. Two recent studies reported that platelet GPVI also functions as fibrin receptor, which would importantly widen the mode of action of GPVI-targeted antithrombotic drugs. We studied the binding of two GPVI fusion proteins to fibrin under static and arterial flow conditions. Fibrin was prepared from purified fibrinogen or generated more physiologically from endogenous fibrinogen by coagulating plasma with thrombin. Fibrin formation was also triggered by exposing TF-coated surfaces or human atherosclerotic plaque slices to arterially flowing blood. By binding studies and advanced optical imaging, we found that recombinant dimeric GPVI-Fc fusion proteins with Fc from either IgG1 (GPVI-Fc1) or IgG2 (GPVI-Fc2) bound to collagen fibres, but neither to fibrin prepared from purified fibrinogen obtained from three suppliers, nor to physiological fibrin formed by thrombin in plasma or triggered by exposing TF or atherosclerotic plaque slices to arterially flowing blood. Our findings do not support a role of dimeric platelet GPVI as receptor for fibrin. This is important for the understanding of plaque-triggered platelet thrombus formation and is clinically relevant for future GPVI-targeting therapies with recombinant GPVI-Fc and anti-GPVI antibodies.

Topics: Atherosclerosis; Blood Coagulation; Blood Platelets; Collagen; Fibrin; Fibrinogen; Humans; Microscopy, Fluorescence; Plaque, Atherosclerotic; Platelet Activation; Platelet Adhesiveness; Platelet Aggregation; Platelet Membrane Glycoproteins; Protein Binding; Protein Multimerization; Recombinant Proteins; Thrombin

As the inflammatory enzyme myeloperoxidase (MPO) is abundant in ruptured human atherosclerotic plaques, we aimed to investigate the role of MPO as a potential diagnostic and therapeutic target for high-risk plaque.. We employed the tandem stenosis model of atherosclerotic plaque instability in apolipoprotein E gene knockout (Apoe-/-) mice. To test the role of MPO, we used Mpo-/-Apoe-/- mice and the 2-thioxanthine MPO inhibitor AZM198. In vivo MPO activity was assessed by liquid chromatography-tandem mass spectrometry detection of 2-chloroethidium generation from hydroethidine and by bis-5HT-DTPA-Gd (MPO-Gd) molecular magnetic resonance imaging (MRI), while plaque phenotype was verified histologically. Myeloperoxidase activity was two-fold greater in plaque with unstable compared with stable phenotype. Genetic deletion of MPO significantly increased fibrous cap thickness, and decreased plaque fibrin and haemosiderin content in plaque with unstable phenotype. AZM198 inhibited MPO activity and it also increased fibrous cap thickness and decreased fibrin and haemosiderin in plaque with unstable phenotype, without affecting lesion monocytes and red blood cell markers or circulating leukocytes and lipids. MPO-Gd MRI demonstrated sustained enhancement of plaque with unstable phenotype on T1-weighted imaging that was two-fold greater than stable plaque and was significantly attenuated by both AZM198 treatment and deletion of the Mpo gene.. Our data implicate MPO in atherosclerotic plaque instability and suggest that non-invasive imaging and pharmacological inhibition of plaque MPO activity hold promise for clinical translation in the management of high-risk coronary artery disease.

Topics: Animals; Atherosclerosis; Disease Models, Animal; Fibrin; Hemosiderin; Magnetic Resonance Imaging; Mass Spectrometry; Mice, Knockout; Molecular Imaging; Peroxidase; Plaque, Atherosclerotic; Thioxanthenes

Atherosclerosis, a chronic vascular disease, leads to molecular events bound with interplaying processes of inflammation and coagulation. In the present study, fibronectin (FN), FN containing extra domain A (EDA-FN), frequency of occurrence, and relative amounts of soluble plasma FN-fibrin complexes were analyzed in 80 plasma samples of patients suspected of coronary artery disease based on clinical evaluation and changes in arteries found by computed tomographic coronary angiography. The study showed that in the plasma of the patients' group with high risk of coronary artery disease EDA-FN concentration was significantly higher (3.5 ± 2.5 mg/L; P < 0.025) and the molecular FN-fibrin complexes of 1000 kDa and higher occurred more often than in the groups of patients with mild risk of coronary artery disease and the normal age-matched. The increased level of EDA-FN and occurrence of FN-fibrin complexes could have a potential diagnostic value in the diagnosis and management of patients with coronary artery disease.

Topics: Atherosclerosis; Cohort Studies; Coronary Artery Disease; Fibrin; Fibronectins; Humans; Risk

It is unclear whether clot composition analysis is helpful to predict a stroke mechanism in acute large vessel occlusion. In addition, the relationship between early vessel signs on imaging studies and clot compositions has been poorly understood. The purpose of this study was to elucidate the relationship between clot composition and stroke etiology following mechanical thrombectomy and to investigate the effect of varied clot compositions on gradient-echo MR imaging of clots.. Histopathologic analysis of retrieved clots from 37 patients with acute MCA occlusion was performed. Patients underwent gradient-echo imaging before endovascular therapy. Retrieved clots underwent semiquantitative proportion analysis to quantify red blood cells, fibrin, platelets, and white blood cells by area. Correlations between clot compositions and stroke subtypes and susceptibility vessel signs on gradient-echo imaging were assessed.. Stroke etiology was classified as cardioembolism in 22 patients (59.4%), large-artery atherosclerosis in 8 (21.6%), and undetermined in 7 (18.9%). The clots from cardioembolism had a significantly higher proportion of red blood cells (37.8% versus 16.9%, P = .031) and a lower proportion of fibrin (32.3% versus 48.5%, P = .044) compared with those from large-artery atherosclerosis. The proportion of red blood cells was significantly higher in clots with a susceptibility vessel sign than in those without it (48.0% versus 1.9%, P < .001), whereas the proportions of fibrin (26.4% versus 57.0%, P < .001) and platelets (22.6% versus 36.9%, P = .011) were significantly higher in clots without a susceptibility vessel sign than those with it.. The histologic composition of clots retrieved from cerebral arteries in patients with acute stroke differs between those with cardioembolism and large-artery atherosclerosis. In addition, a susceptibility vessel sign on gradient-echo imaging is strongly associated with a high proportion of red blood cells and a low proportion of fibrin and platelets in retrieved clots.

Topics: Aged; Aged, 80 and over; Atherosclerosis; Blood Platelets; Erythrocytes; Female; Fibrin; Heart Diseases; Humans; Intracranial Embolism; Leukocytes; Magnetic Resonance Imaging; Male; Middle Aged; Stroke

We related composition of cerebral thrombi to stroke subtype and attenuation on non-contrast CT (NCCT) to gain more insight in etiopathogenesis and to validate thrombus attenuation as a new imaging biomarker for acute stroke.. We histopathologically investigated 22 thrombi retrieved after mechanical thrombectomy in acute stroke patients. First, thrombi were classified as fresh, lytic or organized. Second, percentages of red blood cells (RBCs), platelets and fibrin and number of red, white (respectively RBCs or platelets outnumbering other components with ≥ 15%) or mixed thrombi were compared between large artery atherosclerosis (LAA), cardioembolism, dissection and unknown subtype. Third, correlation between attenuation and RBCs, platelets and fibrin was calculated using Pearson's correlation coefficients (r).. Thrombi were fresh in 73% (n = 16), lytic in 18% (n = 4) and organized in 9% (n = 2). The stroke cause was LAA in eight (36%), cardioembolism in six (27%), dissection in three (14%), and unknown in five (23%) patients. LAA thrombi showed the highest percentage RBCs (median 50 (range 35-90)), followed by dissection (35 (20-40), p = 0.05), cardioembolism (35 (5-45), p = 0.013) and unknown subtype (25 (2-40), p = 0.006). No differences in platelets (p = 0.16) and fibrin (p = 0.52) between subtypes were found. LAA thrombi were classified as red or mixed (both n = 4), cardioembolisms as mixed (n = 5) or white (n = 1) and dissection as mixed (n = 3). There was a moderate positive correlation between attenuation and RBCs (r = 0.401, p = 0.049), and weak negative correlations with platelets (r = -0.368, p = 0.09) and fibrin (r = -0.073, p = 0.75).. The majority of cerebral thrombi is fresh. There are no differences in age of thrombi between subtypes. LAA thrombi have highest percentages RBCs, cardioembolism and unknown subtype lowest. No relationship exists between subtype and platelets or fibrin percentages. We found a correlation between the RBC-component and thrombus attenuation, which improves validation of thrombus attenuation on NCCT as an imaging biomarker for stroke management.

Topics: Aged; Atherosclerosis; Biomarkers; Blood Platelets; Erythrocytes; Female; Fibrin; Humans; Intracranial Thrombosis; Male; Middle Aged; Risk Factors; Stroke; Thrombectomy; Tomography, X-Ray Computed

Coagulation factor XI is proposed as therapeutic target for anticoagulation. However, it is still unclear whether the antithrombotic properties of factor XI inhibitors influence atherosclerotic disease and atherothrombosis. Our aim is to investigate whether factor XI antisense oligonucleotides could prevent thrombus formation on acutely ruptured atherosclerotic plaques.. Atherosclerotic plaques in the carotid arteries of Apoe(-/-) mice were acutely ruptured using ultrasound. The subsequent thrombus formation was visualized and quantified by intravital microscopy and immunohistochemistry. Mice were pretreated with either factor XI antisense or nonsense oligonucleotides (50 mg/kg) to lower factor XI plasma levels. A tail bleeding assay was used to determine the safety. On plaque rupture, initial platelet adhesion and platelet plug formation were not impaired in animals treated with factor XI antisense oligonucleotides. However, the ensuing thrombus formation and fibrin deposition were significantly lower after 5 to 10 minutes (P<0.05) in factor XI antisense oligonucleotide-treated animals without inducing a bleeding tendency. Furthermore, thrombi from antisense-treated animals were less stable than thrombi from placebo-treated animals. Moreover, macrophage infiltration and collagen deposition were lower in the carotid arteries of factor XI antisense-treated animals. No neutrophils were present.. Factor XI antisense oligonucleotides safely prevent thrombus formation on acutely ruptured atherosclerotic plaques in mice. Furthermore, perturbed carotid arteries from factor XI antisense-treated animals show a less severe inflammatory response.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Blood Coagulation; Blood Platelets; Carotid Arteries; Carotid Artery Diseases; Cholesterol, Dietary; Collagen; Disease Models, Animal; Factor XI; Fibrin; Inflammation; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oligonucleotides, Antisense; Plaque, Atherosclerotic; Platelet Adhesiveness; Platelet Aggregation; Rupture, Spontaneous; Thrombosis; Time Factors

To evaluate the effect of a polymer-free Biolimus A9-eluting stent [BioFreedom (BF)], compared with that of a biodegradable polymer-based Biolimus A9-eluting stent [BioMatrix Flex (BMF)] and a bare metal stent (BMS) in balloon denuded and radiated hypercholesterolemic rabbit iliac arteries.. Rabbits were fed with 1% cholesterol diet (n = 14) for 14 days, both iliac arteries were balloon denuded and radiated, and then rabbits were switched to 0.15% cholesterol diet. After 4 weeks, BF (n = 8), BMF (n = 8), and BMS (n = 8) were deployed in denuded and radiated areas. Four weeks later animals were euthanized, arterial segments were processed for morphometry.. The neointimal area in vessels implanted with BF stents was significantly less than that seen in vessels implanted with BMS (0.90 mm(2) ± 0.14 vs. 1.29 mm(2) ± 0.23, P <0.01). Percent fibrin and fibrin score were higher with BMF stents compared to BMS (P <0.03 and <0.04) and giant cell number was significantly higher with both BMF and BF stents (P < 0.01 for both). Percent endothelialization was significantly higher and % uncovered struts were lower with BMS compared to either BMF or BF stents (P < 0.05 for both).. This study demonstrates that compared to BMS, BF stents significantly decreased neointimal hyperplasia.

Topics: Absorbable Implants; Angioplasty, Balloon; Animals; Atherosclerosis; Cardiovascular Agents; Constriction, Pathologic; Disease Models, Animal; Drug-Eluting Stents; Fibrin; Hypercholesterolemia; Hyperplasia; Iliac Artery; Inflammation; Male; Metals; Neointima; Plaque, Atherosclerotic; Polymers; Prosthesis Design; Rabbits; Sirolimus; Stents; Time Factors

Molecular magnetic resonance imaging (MRI) has emerged as a promising non-invasive modality to characterize atherosclerotic vessel wall changes on a morphological and molecular level. Intraplaque and endothelial fibrin has recently been recognized to play an important role in the progression of atherosclerosis. This study aimed to investigate the feasibility of intraplaque and endothelial fibrin detection using a fibrin-targeted contrast-agent, FTCA (EPIX Pharmaceuticals, Lexington, MA), in a mouse model of atherosclerosis.. Male apolipoproteinE-knockout mice (ApoE(-/-)) were fed a high fat diet (HFD) for one to three months. MRI of the brachiocephalic artery was performed prior to and 90 min after the administration of FTCA (n=8 per group). Contrast to noise ratios (CNR) and longitudinal relaxation rates (R1) of plaques were determined and compared to ex vivo fibrin density measurements on immunohistological sections stained with a fibrin-specific antibody and gadolinium concentrations measured by inductively coupled mass spectroscopy (ICP-MS).. Molecular MRI after FTCA administration demonstrated a significant increase (p<0.05) in contrast agent uptake in brachiocephalic artery plaques. In vivo CNR measurements were in good agreement with ex vivo fibrin density measurements on immunohistochemistry (y=2.4x+11.3, R(2)=0.82) and ICP-MS (y=0.95x+7.1, R(2)=0.70). Late stage atherosclerotic plaques displayed the strongest increase in CNR, R1, ex vivo fibrin staining and gadolinium concentration (p<0.05).. This study demonstrated the feasibility of intraplaque and endothelial fibrin imaging using FTCA. Direct in vivo fibrin detection and quantification could be useful for characterization and staging of coronary and carotid atherosclerotic lesions, which may aid diagnosis and intervention.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Contrast Media; Diet, High-Fat; Disease Models, Animal; Endothelium, Vascular; Fibrin; Gadolinium; Magnetic Resonance Imaging; Male; Mice; Peptides; Plaque, Atherosclerotic

Topics: Animals; Apolipoproteins E; Atherosclerosis; Contrast Media; Endothelium, Vascular; Fibrin; Gadolinium; Male; Peptides; Plaque, Atherosclerotic

Topics: Aged; Atherosclerosis; Carotid Intima-Media Thickness; Female; Fibrin; Fibrinogen; Humans; Male; Middle Aged; Risk Factors

Using scanning electron microscopy we analyzed thrombotic material removed from coronary bypass grafts in a 57-year-old woman with multilevel atherosclerosis presenting with acute myocardial infarction (AMI). A white thrombotic material removed from the marginal branch bypass that contained large amounts of activated platelets displaying pseudopodia clearly visible at a higher magnification with a relatively low amount of fibrin. The other thrombus obtained from the right posterior descendent branch (RPD) bypass showed a highly organized fibrin structure composed of thicker fibers with low amounts of cellular components. Our findings indicate that the thrombus structure is different in AMI patients in whom the infarct-related vessel is vein anastomosis compared to those with a native coronary artery occluded. These findings help explain resistance of such thrombi to fibrinolysis and faster plaque growth related to fibrin accumulation.

Topics: Atherosclerosis; Cell Shape; Coronary Artery Bypass; Female; Fibrin; Humans; Microscopy, Electron, Scanning; Middle Aged; Myocardial Infarction; Platelet Activation; Pseudopodia; Thrombosis

The aim of this study was to understand the initial mechanism of arterial thrombus formation induced by vulnerable human atherosclerotic plaques to re-assess and improve current antithrombotic strategies.. Rupture of atherosclerotic plaques causes arterial thrombus formation that might lead to myocardial infarction and ischemic stroke. Atherothrombosis is considered as an inseparable tangle of platelet activation and coagulation processes, involving plaque components such as tissue factor (TF) and collagen as well as blood-borne TF and coagulation factor XIIa (FXIIa). A combination of anticoagulants and antiplatelet agents is the present treatment.. Human atheromatous plaque material was exposed to blood or blood components at physiological calcium/magnesium concentration. Platelet aggregation and coagulation were measured under static and arterial flow conditions by state-of-the-art microscopic and physiological techniques. Plaque TF, plaque collagen, FXIIa, and platelet glycoprotein VI (GPVI) were specifically inhibited.. Plaques induced thrombus formation by 2 discrete steps. The rapid first phase of GPVI-mediated platelet adhesion and aggregation onto plaque collagen occurred within 1 min. The second phase of coagulation started after a delay of >3 min with the formation of thrombin and fibrin, and was driven entirely by plaque TF. Coagulation occurred only in flow niches provided by platelet aggregates, with no evidence for a role of blood-borne TF and FXIIa. Inhibition of GPVI but not plaque TF inhibited plaque-induced thrombus formation.. The major thrombogenic plaque components--collagen and TF--induce platelet activation and coagulation, respectively, in 2 consecutive steps. Targeting specifically the first step is crucial and might be sufficient to inhibit atherothrombus formation.

Topics: Atherosclerosis; Collagen; Female; Fibrin; Humans; Male; Platelet Activation; Platelet Membrane Glycoproteins; Thrombin; Thromboplastin; Thrombosis

Atherothrombosis is a major cause of cardiovascular events. However, animal models to study this process are scarce.. We describe the first murine model of acute thrombus formation upon plaque rupture to study atherothrombosis by intravital fluorescence microscopy.. Localized rupture of an atherosclerotic plaque in a carotid artery from Apoe(-/-) mice was induced in vivo using ultrasound. Rupture of the plaque and formation of localized thrombi were verified by two-photon laser scanning microscopy (TPLSM) in isolated arteries, and by immunohistochemistry. The thrombotic reaction was quantified by intravital fluorescence microscopy.. Inspection of the ultrasound-treated plaques by histochemistry and TPLSM demonstrated local damage, collagen exposure, luminal thrombus formation as well as intra-plaque intrusion of erythrocytes and fibrin. Ultrasound treatment of healthy carotid arteries resulted in endothelial damage and limited platelet adhesion. Real-time intravital fluorescence microscopy demonstrated rapid platelet deposition on plaques and formation of a single thrombus that remained subocclusive. The thrombotic process was antagonized by thrombin inhibition, or by blocking of collagen or adenosine diphosphate receptor pathways. Multiple thrombi were formed in 70% of mice lacking CD40L.. Targeted rupture of murine plaques results in collagen exposure and non-occlusive thrombus formation. The thrombotic process relies on platelet activation as well as on thrombin generation and coagulation, and is sensitive to established and novel antithrombotic medication. This model provides new possibilities to study atherothrombosis in vivo.

Topics: Animals; Atherosclerosis; Blood Coagulation; Blood Platelets; Carotid Artery Thrombosis; Collagen; Disease Models, Animal; Erythrocytes; Fibrin; Mice; Microscopy, Fluorescence; Thrombosis

Atherosclerosis is a chronic inflammatory disease in the vessel. As an inflammatory cytokine, C-reactive protein (CRP) participates in the pathogenesis of atherosclerosis through multiple bioactivities. It has been widely accepted that hyperfibrinogenemia is associated with the formation and progression of atherosclerosis. But, it is unknown whether fibrinogen exerts a pro-inflammatory effect on vascular smooth muscle cells (VSMCs). The purpose of the present study was to observe the effect of fibrinogen, fibrin, and fibrin degradation products (FDP) on CRP generation in VSMCs. CRP mRNA expression was identified with the reverse transcription polymerase chain reaction. CRP level in the supernatant of VSMCs was measured with the enzyme-linked immunosorbent assay. CRP expression in VSMCs was examined with the immunocytochemical method. The results showed that fibrinogen, fibrin, and FDP all induced CRP production in VSMCs both in mRNA level and in protein level in a time- and concentration-dependent manner. The potency is FDP>fibrin>fibrinogen, which seems to mean that their pro-inflammatory activity decreases with increase of molecular weight of these three proteins. The finding provides a new mechanism for atherogenic effect of fibrin(ogen) and FDP, and emphasizes the importance of therapy of hyperfibrinogenemia in atherosclerosis.

Topics: Animals; Atherosclerosis; C-Reactive Protein; Cells, Cultured; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Rats; Rats, Sprague-Dawley

Fibrin-specific molecular targeting strategies are desirable for site-specific imaging and treatment of late stage atheroma, but fibrin-specific antibodies are difficult to produce and present immunogenicity problems. Tissue plasminogen activator (tPA) is an endogenous protein that has been shown to bind fibrin with high affinity and may circumvent antibody difficulties. Use of tPA-derived proteins or peptides, however, requires that the plasminogen-activating proteolytic activity be neutralized or removed. As an initial step in determining the feasibility of this targeting strategy, human recombinant tPA (Activase) was irreversibly inhibited with D-phe-L-pro-L-arg-chloromethyl ketone (PPACK) and conjugated to intrinsically echogenic liposomes (ELIP) by a thioether coupling protocol. Fibrin-binding affinities were assessed with a novel two-stage fibrin pad ELISA. We achieved 95-99% inactivation, while retaining both tPA fibrin-binding activities of K(D) approximately 2 nM and 33 nM. Thermodynamic analysis of the PPACK-inactivated tPA (tPA(P)) revealed highly exothermic interactions, indicative of ionic associations, especially for the higher affinity. The conjugation efficiency of tPA(P) to ELIP was within the range of that previously achieved for IgG and exhibited satisfactory fibrin targeting, characterized by striking increases of enthalpy and entropy increments. Evidence for coupling of noncovalent association energetics with the phosphatidylethanolamine major phase transition, observed in previous IgG antibody conjugations, was also evident in this case, but the nature of the transduction mechanism was different. These results demonstrate that tPA-derived components lacking proteolytic activity can be employed as fibrin-targeting agents for delivery of therapeutic and diagnostic formulations.

Topics: Amino Acid Chloromethyl Ketones; Animals; Antibodies; Antibody Affinity; Atherosclerosis; Contrast Media; Drug Delivery Systems; Enzyme Activation; Fibrin; Fibrinolytic Agents; Humans; Liposomes; Serine Proteinase Inhibitors; Tissue Plasminogen Activator; Ultrasonography

Collagen Type I and fibrin are polymeric proteins commonly used in the field of regenerative medicine as the foundational matrix of engineered tissues. We examined the response of vascular smooth muscle cells (VSMC) to both two-dimensional (2D) substrates as well as three-dimensional (3D) matrices of these biopolymers. Pure collagen Type I, pure fibrin and composite matrices consisting of 1:1 mixtures of collagen and fibrin were studied. Relative gene expression of three ECM molecules (collagen Type I and III, and tropoelastin) and three integrin subunits (integrins alpha1, beta1 and beta3) was determined over 7 days in culture using quantitative RT-PCR. Expression of all of these marker genes was up-regulated in 3D matrices, relative to 2D substrates. Tropoelastin, integrin alpha1 and integrin beta1 were highest in collagen matrices, while collagen III and integrin beta3 expression were highest in pure fibrin, and collagen I expression was highest in the collagen-fibrin composite materials. Both the compositional and temporal expression patterns of these specific ECM-related genes were suggestive of a wound healing response. These results illuminate the short-term responses of VSMC to 2D and 3D biopolymer matrices, and have relevance to tissue engineering and cardiovascular biology.

Topics: Animals; Atherosclerosis; Cells, Cultured; Collagen; Extracellular Matrix; Fibrin; Gene Expression Regulation; Hydrogels; Hypertension; Integrins; Male; Muscle, Smooth, Vascular; Rats; Tissue Engineering; Tropoelastin

1. Fibrin D-dimer is considered a consistent and independent marker of the risk of cardiovascular disease in population studies, as well as being related to atherosclerosis severity in patients. However, the role of fibrin D-dimer in macrophage-derived foam cell formation during atherogenesis remains unclear. 2. In the present study, using microarray techniques, we determined the effects of 100 ng/mL fibrin D-dimer fragments on macrophage cell function in atherosclerosis by investigating the expression levels of 128 genes related to the atherosclerotic pathophysiological processes. 3. The results showed that 27 genes were enhanced by D-dimer fragments to over twofold of control. These 27 genes belonged to six groups and included adhesion molecules, extracellular molecules, molecules related to lipid transport and metabolism, cell growth and proliferation molecules, transcription regulators and genes responsive to stress. We proceeded to determine the expression levels of five of these genes (intercellular adhesion molecule-1, matrix metalloproteinase-9, oxidized low-density lipoprotein receptor 1, vascular endothelial growth factor A and peroxisome proliferator-activated receptor alpha) using SYBR real-time polymerase chain reaction. The results confirmed gene upregulation, similar to the results obtained with the microarray, following treatment with D-dimer. 4. Therefore, the present study provides direct evidence regarding the pro-atherosclerotic role of D-dimer in macrophage function, which is mainly to enhance the inflammatory response during macrophage-derived foam cell formation.

Topics: Atherosclerosis; Cell Adhesion Molecules; Cell Proliferation; Fibrin; Gene Expression Regulation; Gene Library; Humans; Indicators and Reagents; Inflammation; Lipid Metabolism; Macrophages; Nucleic Acid Hybridization; Oligonucleotide Array Sequence Analysis; Oxidative Stress; Reverse Transcriptase Polymerase Chain Reaction; RNA; U937 Cells; Up-Regulation

The extracellular matrix protein osteopontin (OPN) plays a nonredundant role in atherosclerosis and restenosis. Here we investigated the impact of OPN up-regulation in an in vitro model of re-endothelialization after mechanical injury of the endothelial cell monolayer. Murine aortic endothelial (MAE) cells interact via alpha(v) integrins with the integrin-binding Arg-Gly-Asp OPN sequence and adhere to immobilized OPN. On this basis, MAE cells were stably transfected with a wild-type OPN cDNA (OPN-MAE cells), with an OPN mutant lacking the Arg-Gly-Asp sequence (DeltaRGD-OPN-MAE cells), or with vector alone (mock-MAE cells). When compared with mock-MAE and DeltaRGD-OPN-MAE cells, OPN-MAE cells showed a reduced sprouting activity in fibrin gel, a reduced motility in a Boyden chamber assay, and a reduced capacity to repair the wounded monolayer. Accordingly, OPN-MAE cells at the edge of the wound were unable to form membrane ruffles, to reorganize their cytoskeleton, and to activate the focal adhesion kinase and the small GTPase Rac1, key regulators of the cell entry into the first phase of the cell migration cycle. Accordingly, wounded OPN-MAE cells failed to activate the intracellular signals RhoA and ERK1/2, involved in the later phases of the cell migration cycle. Also, parental MAE cells showed reduced re-endothelialization after wounding when seeded on immobilized OPN and exhibited increased adhesiveness to OPN-enriched extracellular matrix. In conclusion, OPN up-regulation impairs re-endothelialization by inhibiting the first phase of the cell migration cycle via alpha(v) integrin engagement by the extracellular matrix-immobilized protein. This may contribute to the adverse effects exerted by OPN in restenosis and atherosclerosis.

Topics: Animals; Aorta; Atherosclerosis; Cell Line, Transformed; Cell Movement; Endothelial Cells; Extracellular Matrix; Fibrin; Focal Adhesion Protein-Tyrosine Kinases; Graft Occlusion, Vascular; Integrin alphaV; MAP Kinase Signaling System; Mice; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mutation; Neuropeptides; Osteopontin; rac GTP-Binding Proteins; rac1 GTP-Binding Protein; Recombinant Proteins; Transfection

Urokinase plasminogen activator (uPA) is strongly expressed in atherosclerotic lesions, but the overall effect of the protease on plaque composition and growth remains controversial. In the present study, apolipoprotein E-deficient (apoE(-/-)) mice were intercrossed with mice which were lacking the uPA gene (doubleknockout; DKO). In ferric chloride-induced carotid artery lesions in chow-fed mice, uPA deficiency increased neointimal size (P = 0.015) and luminal stenosis (P = 0.014), while reducing media thickness (P = 0.002). A lack of uPA also increased the size of and the luminal obstruction from atherosclerotic plaques at the coronary and brachiocephalic arteries of apoE(-/-) mice. Plaques were characterised by a higher fibrinogen/fibrin content and a decrease in cellularity and collagen content. When apoE(-/-) and DKO mice were analysed as a single group, a significant correlation was found between the alpha-actin (smooth muscle cell) and collagen content of atherosclerotic lesions (r = 0.554; P < 0.05), and a negative correlation existed between the alpha-actin and fibrin/fibrinogen immunopositive area (r = -0.791; P < 0.001). Further analysis of brachiocephalic atherosclerosis, a predilection site for plaque rupture in the apoE(-/-) mouse, revealed signs of plaque vulnerability, including a reduced cap-to-intima ratio (0.21 +/- 0.04 vs. 0.37 +/- 0.05; P = 0.03) and more frequent detection of intraplaque haemorrhage (56% vs. 13%; P < 0.01) and buried fibrous caps (1.8 +/- 0.5 vs. 0.5 +/- 0.2; P = 0.02) in DKO compared to apoE(-/-) mice. These results indicate that, at least at (patho)physiologic concentrations, uPA is essential for maintaining the cellularity and collagen content and, possibly, the stability of lesions, both by preventing excessive intramural fibrin accumulation and by facilitating cell migration and invasion.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Carotid Artery Diseases; Cell Movement; Collagen; Disease Progression; Fibrin; Hemorrhage; Mice; Mice, Knockout; Urokinase-Type Plasminogen Activator

Apolipoprotein A-I (apoA-I), the major protein constituent within high-density lipoprotein (HDL), has been associated with antiatherogenic protection by mechanisms that include reverse cholesterol transport and antiinflammatory functions. To evaluate the proposed protective function of apoA-I, proteins modified by nitrating oxidants were evaluated in the aortic tissue and plasma of mice lacking the low-density lipoprotein receptor and apobec (LA) and LA mice with genetic deletion of apoA-I (LA-apoA-I(-/-)). The levels of nitrated proteins in aortic tissue quantified by liquid chromatography with online electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS) were 6-fold higher in the LA-apoA-I(-/-) as compared with the LA mice. The quantitative analyses were corroborated by immunohistochemical and high-resolution immunoelectron microscopic evaluation of the lesions, which revealed abundant staining for nitrated proteins in the aortic root lesions of LA-apoA-I(-/-) as compared with the LA mice. Proteomic approaches based on affinity enrichment and site-specific adduct mapping identified unique specific protein targets for nitration in the plasma of LA-apoA-I(-/-) that were not present in the plasma of LA mice. In particular the nitration of fibrinogen was shown to accelerate fibrin clot formation. Another consequence of the augmented levels of nitrated proteins was the induction of humoral responses documented by the increased circulating immunoglobulins that recognize nitrotyrosine in LA-apoA-I(-/-) as compared with the LA mice. These data collectively support a protective function of apoA-I diminishing the burden of nitrative oxidants in these mice models of atherosclerosis.

Topics: Animals; Aorta; Apolipoprotein A-I; Atherosclerosis; Autoantibodies; Blood Coagulation; Blood Proteins; Cholesterol, HDL; Disease Models, Animal; Female; Fibrin; Fibrinogen; Immunohistochemistry; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Immunoelectron; Nitrogen; Oxidants; Proteomics; Tyrosine

Besides having a key role in fibrinolysis, the plasminogen system has been implicated in cell migration and angiogenesis. A common mechanism is the binding of plasminogen to carboxy-terminal lysine residues in partially degraded fibrin or on cellular surfaces. Here we examined the involvement of thrombin activatable fibrinolysis inhibitor (TAFI) and pancreatic carboxypeptidase B (CPB) in an in vitro capillary tube formation system, which is largely plasminogen-dependent.. Human microvascular endothelial cells (hMVECs) were seeded on a 3D plasma clot matrix and subsequently stimulated with bFGF/tumor necrosis factor (TNF)-alpha. Tube formation was analyzed and fibrin degradation products (FbDP) were determined in the medium. Supplementation of the matrix with additional TAFI or CPB produced a reduction in tube formation. Pretreatment of hMVECs with CPB before seeding resulted in a similar effect. FbDP-levels indicated a concomitant reduction in matrix proteolysis. A TAFIa inhibitor increased tube formation and FbDP release into the medium. In separate assays, CPB impaired the migration of hMVECs in a dose-dependent manner, whereas proliferation and adhesion remained unaffected.. Overall, these results demonstrate that TAFI and CPB in these systems modulate the plasminogen system both in the matrix and on the cell surface, thus leading to the inhibition of endothelial cell movement and tube formation.

Topics: Angiogenesis Inhibitors; Atherosclerosis; Capillaries; Carboxypeptidase B; Carboxypeptidase B2; Cell Adhesion; Cell Culture Techniques; Cell Movement; Cell Proliferation; Cells, Cultured; Dose-Response Relationship, Drug; Endothelial Cells; Fibrin; Fibrin Fibrinogen Degradation Products; Fibroblast Growth Factor 2; Humans; Neovascularization, Physiologic; Plant Proteins; Plasminogen; Protease Inhibitors; Time Factors; Tumor Necrosis Factor-alpha; Urokinase-Type Plasminogen Activator; Wound Healing

For the study of atherogenesis in vitro, coculture systems have been devised, in which two or more cell types can be cultured in close contact to each other. Herein, we describe a novel in vitro model that aims at the simulation of the morphology of a normal muscular artery allowing for the study of the initial events in atherosclerosis. Using a modified fibrin gel as a scaffold for the coculture of endothelial cells (ECs) and smooth muscle cells (SMCs), we generated an autologous in vitro model with a multilayer growth of SMCs (intima-like structure) covered by an endothelium. The production of extracellular matrix (ECM) could be visualized histologically and verified by (i) ascorbic-acid dependent secretion of procollagen I into the supernatant and (ii) deposition of collagens I and III as well as laminin in the gel as assessed by immunohistochemistry. By BrdU-incorporation and Ki67 expression, the SMCs exhibited minimal proliferative activity, even when the culture period was extended to 6 weeks. Lipoprotein insudation was investigated under simulated hypo-, normo- and hypercholesterolemic conditions through addition of 0.5, 1 or 2 mg/mL LDL to the medium with subsequent time and dose dependent insudation of LDL. When human monocytes were added to the culture medium, infiltration and foam cell formation of macrophages and SMCs as well as expression of interleukin-8 (IL-8) was demonstrated. The in vitro model of the human vascular wall described herein appears to be suitable for the study of pivotal events in atherosclerotic plaque development. The applicability for long-term culture, the ability to study cell-matrix interactions and the opportunities for histomorphological and immunohistochemical examinations represent additional advantages of this model.

Topics: Atherosclerosis; Cell Adhesion; Cell Differentiation; Cell Line; Cell Movement; Coculture Techniques; Dose-Response Relationship, Drug; Endothelial Cells; Extracellular Matrix; Fibrin; Foam Cells; Gels; Humans; Lipoproteins, LDL; Monocytes; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Time Factors

Protected carotid artery stent placement is currently under clinical evaluation as a potential alternative to carotid endarterectomy. The current study was undertaken to determine the incidence of new ischemic lesions found on diffusion-weighted MR imaging (DWI) in nonselected patients after protected carotid artery stent placement using a filter device and to determine the potential relationship between these new ischemic lesions and the presence or absence of a clear amount of debris captured by the neuroprotection filter device.. A nonrandomized cohort of 52 patients (40 men, 12 women) presenting with carotid occlusive disease underwent protected carotid artery stent placement using a filter device. DWI obtained 1 day before stent placement was compared with that obtained 1 day after stent placement. In addition, the macroscopic and microscopic analysis of debris captured by the filter device during the carotid stent placement procedure was assessed.. Neuroprotected carotid stent placement was technically successful in all 53 procedures but was complicated by a transient ischemic attack in 3 patients (5.6%). In 22 patients (41.5%), new ischemic lesions were found on DWI, and in 21 filter devices (39.6%), a substantial amount of atheromatous plaque and/or fibrin was found. No clear relationship between the presence of debris captured by the filter device and new lesions detected by DWI was found (P = .087; odds ratio 3.067).. Neuroprotected carotid artery stent placement will not avoid silent cerebral ischemia. Systematic microscopic analysis of debris captured by the filter device has no predictive value for potential cerebral ischemia after carotid artery stent placement.

Topics: Aged; Aged, 80 and over; Atherosclerosis; Brain Ischemia; Carotid Artery, Common; Carotid Stenosis; Cohort Studies; Diffusion Magnetic Resonance Imaging; Equipment Design; Equipment Failure; Female; Fibrin; Filtration; Humans; Male; Membranes, Artificial; Middle Aged; Polyurethanes; Prospective Studies; Risk Factors; Stents

Topics: Arteriosclerosis; Atherosclerosis; Electrons; Fibrin; gamma-Globulins; Microscopy; Microscopy, Electron; Pathology

Topics: Arteriosclerosis; Atherosclerosis; Blood Coagulation; Fibrin; Humans

Topics: Animals; Antibodies; Aortic Diseases; Arteriosclerosis; Atherosclerosis; Fibrin; Fluorescent Antibody Technique; Freund's Adjuvant; Immune Sera; Immunoelectrophoresis; Rabbits; Research; Serum Albumin; Serum Globulins

Topics: Aorta; Arteriosclerosis; Atherosclerosis; Fibrin; Humans; Leukocytes; Thrombosis

Topics: Arteriosclerosis; Atherosclerosis; Coronary Disease; Fibrin; Fibrinolysin; Humans; Thrombosis

Topics: Animals; Aorta; Atherosclerosis; Blood Coagulation; Fibrin; Fibrinolysis; Hemostasis; Hemostatics; Humans