159 research outputs found

    Thrombin generation in human coronary arteries after percutaneous transluminal balloon angioplasty

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    AbstractObjectives. The aim of this study was to investigate the relation between coronary atherosclerotic plaque injury and activation of the coagulation cascade.Background. Thrombus formation after atherosclerotic plaque disruption has been implicated in the pathogenesis of atherosclerosis, unstable angina and myocardial infarction.Methods. Biochemical markers of thrombin generation (prothrombin fragment F1+2) and thrombin activity (fibrinopeptide A) were measured in coronary blood before, during and immediately after percutaneous transluminal coronary angioplasty. After demonstrating that blood withdrawal through an angioplasty catheter does not artifactually elevate the plasma levels of these markers in patients after heparinization, coronary artery samples ware collected proximal and distal to the lesion before and distal to the lesion after baltoon inflation in 26 patients.Results. Plasma levels of F1+2measured proximal to the lesion before angioplasty (median 0.47 nmol/liter, 95% confidence interval [CI] 0.40 to 0.50) were significantly elevated after angioplasty (median 0.55 nmol/liter, 95% CI 0.46 to 0.72, p = 0.001). In contrast, plasma fibrinopeptide A levels measured proximal to the lesion before angioplasty (median 2.0 ng/ml, 95% CI 1.3 to 22) were similar to those measured after angioplasty (median 1.8 ng/ml, 95% CI 1.3 to 3.0, p = NS). After we defined a normal range of interassay variability on the basis of values obtained from samples drawn proximal and distal to the lesion before angioplasty, seven patients (27%) had a significant increase in F1+2plasma levels. A significant increase in plasma fibrinopeptide A occurred in five of these seven patients. Lesions with dissection, filling defects or haziness on postangioplasty angiography were associated with more thrombin generation than lesions without these features.Conclusions. Markers of thrombio generation and activity can be collected safely and assayed accurately in heparinized blood withdrawn through aa angioplasty catheter. Balloon dilation of coronary stenoses increases thrombin generation and activity within the coronary artery in a substantial subgroup of patients undergoing angioplasty

    Association of Altered Collagen Content and Lysyl Oxidase Expression in Degenerative Mitral Valve Disease

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    Background—Collagen cross-linking is mediated by lysyl oxidase (LOX) enzyme in the extracellular matrix (ECM) of mitral valve leaflets. Alterations in collagen content and LOX protein expression in the ECM of degenerative mitral valve may enhance leaflet expansion and disease severity. Methods—Twenty posterior degenerative mitral valve leaflets from patients with severe mitral regurgitation were obtained at surgery. Five normal posterior mitral valve leaflets procured during autopsy served as controls. Valvular interstitial cells (VICs) density was quantified by immunohistochemistry, collagen types I and III by picro-sirius red staining and immunohistochemistry, and proteoglycans by alcian blue staining. Protein expression of LOX and its mediator TGFβ1 were quantified by immunofluorescence and gene expression by PCR. Results—VICs density was increased, structural type I collagen density was reduced, while reparative type III collagen and proteoglycan densities were increased (p \u3c 0.0001) with an increase in spongiosa layer thickness in myxomatous valves. These changes were associated with a reduction in LOX (p \u3c 0.0001) and increase in TGFβ1 protein expression (p \u3c 0.0001). However, no significant change was seen in gene expression. Linear regression analysis identified a correlation between type I collagen density and LOX grade (R2 = 0.855; p \u3c 0.0001). Conclusions—Reduced type I collagen density with a simultaneous increase in type III collagen and proteoglycan densities possibly contributes to spongiosa layer expansion resulting in incompetent mitral valve leaflets. Observed changes in type I and III collagen densities in DMVD may be secondary to alterations in LOX protein expression, contributing to disorganization of ECM and disease severity

    Duration of Dual Antiplatelet Therapy Following Drug-Eluting Stent Implantation in Diabetic and Non-Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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    Background: Diabetic patients account for an increasing number of patients undergoing percutaneous coronary intervention (PCI). However, diabetes mellitus (DM) is associated with increased residual platelet activity during dual antiplatelet treatment (DAPT) and DM patients have worse clinical outcomes after PCI as compared to non DM
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