Increased thrombin generation in persons with echogenic carotid plaques

2008 ◽  
Vol 99 (03) ◽  
pp. 602-608 ◽  
Author(s):  
Ellisiv Mathiesen ◽  
Bjarne Østerud ◽  
Jean Amiral ◽  
Anne Vissac ◽  
John-Bjarne Hansen ◽  
...  
Keyword(s):  
Carotid Stenosis ◽  
Health Survey ◽  
Thrombin Generation ◽  
Plaque Morphology ◽  
Atherosclerotic Plaques ◽  
Blood Samples ◽  
Carotid Plaques ◽  
Prothrombin Fragment ◽  
Cerebrovascular Events ◽  
Diameter Reduction

SummaryEcholucent carotid plaques are associated with higher risk for future ischemic cerebrovascular events (CVE) than echogenic plaques independent of the degree of stenosis.Elevated markers of thrombin generation are associated with atherosclerotic plaques and are increased in the acute and chronic phases of CVE. The present study was conducted to investigate the influence of plaque morphology on thrombin generation in persons with carotid stenosis. One hundred twenty-eight persons with carotid stenosis (≥35% lumen diameter reduction) and 136 matched controls without stenosis were recruited from the health survey of the Tromsø Study. Blood samples were collected and plaque morphology determined by ultrasonography. Thrombin generation was assessed by thrombin-antithrombin complexes (TAT) and by prothrombin fragment 1+2 (F1+2).Persons with echogenic plaques (n=63) had significantly higher levels of TAT (5.24 μg/l, 4.33–6.14) (mean, 95%CI) than persons with echolucent plaques (n=65) (3.44 μg/l, 2.91–3.96, p<0.001) and controls (n=136) (3.33 μg/l, 3.06–3.60, p<0.001).They also had significantly higher levels of F1+2 (2.14 nM, 1.83–2.45) than persons with echolucent plaques (1.54 nM, 1.38–1.71, p<0.001) and controls (1.49 nM, 1.40–1.58, p<0.001). TAT and F1+2 increased linearly with plaque echogenicity (p=0.002 and p=0.001, respectively) independent of the degree of stenosis. Increased thrombin generation was associated with a significant increase in plasma factorV levels among persons with echogenic plaques compared to echolucent plaques (p=0.049) and controls (p=0.025). The present findings indicate that increasing plaque echogenicity, rather than plaque echolucency and the degree of stenosis, is associated with thrombin generation in persons with carotid stenosis.

Expression and Cellular Localization of CXCR4 and CXCL12 in Human Carotid Atherosclerotic Plaques

2018 ◽  
Vol 118 (01) ◽  
pp. 195-206 ◽  
Author(s):  
Sophie Merckelbach ◽  
Emiel van der Vorst ◽  
Michael Kallmayer ◽  
Christoph Rischpler ◽  
Rainer Burgkart ◽  
...  
Keyword(s):  
Protein Level ◽  
Cellular Localization ◽  
Mrna Level ◽  
Plaque Morphology ◽  
Atherosclerotic Plaques ◽  
Cxcl12 Expression ◽  
Carotid Plaques ◽  
Unstable Plaques ◽  
Human Carotid

Background and Aims The CXCR4/CXCL12 complex has already been associated with progression of atherosclerosis; however, its exact role is yet unknown. The aim of this study was to analyse the expression and cellular localization of CXCL12 and its receptor CXCR4 in human carotid atherosclerotic plaques. Methods Carotid plaques (n = 58; 31 stable, 27 unstable, based on histological characterization of plaque morphology) were obtained during carotid endarterectomy, and 10 healthy vessels were used as a control. Expression of cxcr4, cxcr7, cxcl12, ccl2/ccr2 and csf1/csf1r was analysed at mRNA, and level expression of CXCR4, CXCR7 and CXCL12 was analysed at protein level. Cellular localization was determined using consecutive and double immunohistochemical (IHC) staining and microdissection. Results At mRNA level, cxcr4, cxcr7 and cxcl12 were significantly higher expressed in stable carotid plaques compared with controls (p = 0.011, p < 0.001 and p < 0.001). Cxcl12 mRNA expression was successively augmented toward unstable plaques (p < 0.001). At protein level, CXCR4, CXCR7 and CXCL12 expression was significantly increased in both stable (p = 0.001, p < 0.001 and p = 0.035, respectively) and unstable (p = 0.003, p < 0.001 and p = 0.045, respectively) plaques compared with controls. Using IHC, CXCR4 was particularly localized in macrophages and small neovessels. Microdissection confirmed strongest expression of cxcr4 in macrophages within atherosclerotic plaques. Leukocytes and smooth muscle cells showed cxcr4 expression as well. For cxcl12, only microdissected areas with macrophages were positive. Conclusion Expression of CXCR4 and CXCL12 was significantly increased in both stable and unstable carotid atherosclerotic plaques compared with healthy vessels, both at mRNA and protein level. CXCR4 and CXCL12 were localized particularly in macrophages.

scholarly journals Characteristics of Unstable Carotid Plaques – New Image Modalities

Folia Medica ◽  
2019 ◽  
Vol 61 (1) ◽  
pp. 26-33
Author(s):  
Marieta V. Peycheva ◽  
Zahari I. Zahariev ◽  
Kichka G. Velkova ◽  
Lyubomir Chervenkov
Keyword(s):  
Carotid Atherosclerosis ◽  
Shear Wave Elastography ◽  
Plaque Morphology ◽  
Carotid Plaques ◽  
Plaque Instability ◽  
Atherosclerotic Burden ◽  
Personal Management ◽  
Cerebrovascular Events ◽  
Superb Microvascular Imaging ◽  
Microvascular Imaging

Abstract Ischemic stroke is a socially significant health problem due to high mortality and disability. One of the leading causes for cerebrovascular accidents is the carotid atherosclerosis. The mechanism of its formation presents not only lipid accumulation in the arterial wall but a complex inflammatory disease. The aims of this review are to point the new methods and approaches for diagnostic of the unstable and high-risk carotid plaques. The old plaque imaging modalities emphasized mainly to the degrees of luminal stenosis. The new possibilities reveal plaque morphology so detailed even compared to histological verification. Recent techniques as Shear wave elastography, optical coherence tomography, Superb microvascular imaging, USPIO MRI give information about the pathological mechanisms of carotid atherosclerosis. The efforts are directed to predict the atherosclerotic burden, plaque instability and the occurrence of cerebrovascular events for each patient and to optimize personal management.

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.

Abstract 53: Development of Standardized Approach in Symptomatic Carotid Stenosis for Early Intervention

2012 ◽  
Vol 5 (suppl_1) ◽  
Author(s):  
Paola De Rango ◽  
Massimo Lenti ◽  
Valeria Caso ◽  
Enrico Cieri ◽  
Gioele Simonte ◽  
...  
Keyword(s):  
Carotid Stenosis ◽  
Medical Therapy ◽  
Duplex Ultrasound ◽  
Recurrence Risk ◽  
Neurological Status ◽  
Plaque Morphology ◽  
Vascular Surgeon ◽  
Symptomatic Carotid ◽  
Cerebrovascular Events ◽  
Symptomatic Carotid Stenosis

Background: Despite current guidelines recommend performing carotid endarterectomy (CEA) within the first 7-14 days from symptoms onset, this is not the routine approach for symptomatic carotid stenosis in most countries because of logistic difficulties and concerns regarding perioperative risk of “urgent CEA”. The aim of this study was to implement a multi-service in-hospital protocol to standardize the approach and reduce recurrence risk in acute symptomatic carotid stenosis without radical logistic reorganizations. Methods: All patients referred to the Emergency Room (ER) for acute cerebrovascular events will be seen within 24hours by the neurovascular specialist on call who rapidly triages patients (ABCD2 score), starts optimum medical therapy and performs carotid duplex ultrasound in the ER where immediate cerebral imaging will be also done by the neuroradiologist on call. Patients with 50-99% stenosis are discussed with the vascular surgeon on call and treatment decided (CEA vs stenting vs medical therapy) according to patients’ comorbidities, neurological status and carotid plaque morphology. Decision for intervention implies immediate transferal to the Vascular Surgery Unit where treatment is guaranteed within 2-48 hours in a hybrid operating room. The neurovascular specialist follows all postoperative courses (eventual transferal to Stroke Unit can be decided). Results: Before the application of the standardized protocol, over 2002 consecutive carotid interventions, 684 were performed for symptomatic stenosis with perioperative stroke/death risk of 3.5%, similar in Stenting and CEA. The stroke risk at 5 years after the procedure was 8.7% after CEA vs. 4.9% after stenting (p =0.7). However, there was extreme variability in symptoms-to-treatment delay. Conclusion: Multidisciplinary team collaboration among traditional 24h availability local services would standardize the approach to carotid stenosis in symptomatic patients without substantially changes in hospital services and relevant logistic reorganization. The efficacy of stenting in early treatment will be verified. Increased prevalence of symptomatic interventions and improved stroke prevention rates are expected with the new protocol.

Matrix metalloproteinase-2 of human carotid atherosclerotic plaques promotes platelet activation

2014 ◽  
Vol 111 (06) ◽  
pp. 1089-1101 ◽  
Author(s):  
Massimo Lenti ◽  
Emanuela Falcinelli ◽  
Marcella Pompili ◽  
Paola De Rango ◽  
Valentina Conti ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Matrix Metalloproteinase ◽  
Platelet Activation ◽  
Matrix Metalloproteinase 2 ◽  
Atherosclerotic Plaques ◽  
Active Matrix ◽  
Carotid Plaques ◽  
Cerebrovascular Events ◽  
Human Carotid

SummaryPurified active matrix metalloproteinase-2 (MMP-2) is able to promote platelet aggregation. We aimed to assess the role of MMP-2 expressed in atherosclerotic plaques in the platelet-activating potential of human carotid plaques and its correlation with ischaemic events. Carotid plaques from 81 patients undergoing endarterectomy were tested for pro-MMP-2 and TIMP-2 content by zymography and ELISA. Plaque extracts were incubated with gel-filtered platelets from healthy volunteers for 2 minutes before the addition of a subthreshold concentration of thrombin receptor activating peptide-6 (TRAP-6) and aggregation was assessed. Moreover, platelet deposition on plaque extracts immobilised on plastic coverslips under high shear-rate flow conditions was measured. Forty-three plaque extracts (53%) potentiated platelet aggregation (+233 ± 26.8%), an effect prevented by three different specific MMP-2 inhibitors (inhibitor II, TIMP-2, moAb anti-MMP-2). The pro-MMP-2/TIMP-2 ratio of plaques potentiating platelet aggregation was significantly higher than that of plaques not potentiating it (3.67 ± 1.21 vs 1.01 ± 0.43, p<0.05). Moreover, the platelet aggregation-potentiating effect, the active-MMP-2 content and the active MMP-2/pro-MMP-2 ratio of plaque extracts were significantly higher in plaques from patients who developed a subsequent major cardiovascular event. In conclusion, atherosclerotic plaques exert a prothrombotic effect by potentiating platelet activation due to their content of MMP-2; an elevated MMP-2 activity in plaques is associated with a higher rate of subsequent ischaemic cerebrovascular events.

scholarly journals Anti-Apolipoprotein A-1 IgG Influences Neutrophil Extracellular Trap Content at Distinct Regions of Human Carotid Plaques

2020 ◽  
Vol 21 (20) ◽  
pp. 7721
Author(s):  
Rafaela da Silva ◽  
Daniela Baptista ◽  
Aline Roth ◽  
Kapka Miteva ◽  
Fabienne Burger ◽  
...  
Keyword(s):  
Carotid Stenosis ◽  
Experimental Atherosclerosis ◽  
Neutrophil Extracellular Trap ◽  
Atherosclerotic Plaques ◽  
Carotid Plaques ◽  
Apolipoprotein A ◽  
Artery Segment ◽  
Enhanced Expression ◽  
And Function ◽  
Human Carotid

Background: Neutrophils accumulate in atherosclerotic plaques. Neutrophil extracellular traps (NET) were recently identified in experimental atherosclerosis and in complex human lesions. However, not much is known about the NET marker citrullinated histone-3 (H3Cit) expression and functionality in human carotid plaques. Moreover, the association between the proatherosclerotic autoantibody anti-apolipoprotein A-1 (anti-ApoA-1 IgG) and NET has never been investigated. Methods: Atherosclerotic plaques have been obtained from 36 patients with severe carotid stenosis that underwent carotid endarterectomy for severe carotid stenosis. Samples were sectioned into upstream and downstream regions from the same artery segment. Plaque composition and expression of NET markers neutrophil elastase (NE) and H3Cit were quantified by immunohistochemistry. H3Cit expression and function was evaluated by immunofluorescence and confocal analysis in a subset of patients. Results: Pathological features of vulnerable phenotypes were exacerbated in plaques developed at downstream regions, including higher accumulation of neutrophils and enhanced expression of NE and H3Cit, as compared to plaques from upstream regions. The H3Cit signal was also more intense in downstream regions, with significant extracellular distribution in spaces outside of neutrophils. The percentage of H3Cit colocalization with CD66b (neutrophils) was markedly lower in downstream portions of carotid plaques, confirming the extrusion of NET in this region. In agreement, the maximum distance of the H3Cit signal from neutrophils, extrapolated from vortex distance calculation in all possible directions, was also higher in downstream plaques. The serum anti-ApoA-1index positively correlated with the expression of H3Cit in downstream segments of plaques. Expression of the H3Cit signal outside of neutrophils and H3Cit maximal distance from CD66b-positive cells increased in plaques from serum positive anti-ApoA-1 patients compared with serum negative patients. Conclusion: NET elements are differentially expressed in upstream versus downstream regions of human carotid plaques and may be influenced by circulating levels of anti-ApoA-1 IgG. These findings could warrant the investigation of NET elements as potential markers of vulnerability.

scholarly journals Statin Treatment Is Associated with Reduction in Serum Levels of Receptor Activator of NF-κB Ligand and Neutrophil Activation in Patients with Severe Carotid Stenosis

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Sébastien Lenglet ◽  
Alessandra Quercioli ◽  
Mathias Fabre ◽  
Katia Galan ◽  
Graziano Pelli ◽  
...  
Keyword(s):  
Carotid Stenosis ◽  
Neutrophil Infiltration ◽  
Serum Levels ◽  
Statin Treatment ◽  
Atherosclerotic Plaques ◽  
Mrna Levels ◽  
Carotid Plaques ◽  
Receptor Activator ◽  
Patient Groups ◽  
Serum Rankl

Systemic and intraplaque biomarkers have been widely investigated in clinical cohorts as promising surrogate parameters of cardiovascular vulnerability. In this pilot study, we investigated if systemic and intraplaque levels of calcification biomarkers were affected by treatment with a statin in a cohort of patients with severe carotid stenosis and being asymptomatic for ischemic stroke. Patients on statin therapy had reduced serum osteopontin (OPN), RANKL/osteoprotegerin (OPG) ratio, and MMP-9/pro-MMP-9 activity as compared to untreated patients. Statin-treated patients exhibited increased levels of collagen and reduced neutrophil infiltration in downstream portions of carotid plaques as compared to untreated controls. In upstream plaque portions, OPG content was increased in statin-treated patients as compared to controls. Other histological parameters (such as lipid, macrophage, smooth muscle cell, and MMP-9 content) as well as RANKL, RANK, and OPG mRNA levels did not differ between the two patient groups. Serum RANKL/OPG ratio positively correlated with serum levels of neutrophilic products, intraplaque neutrophil, and MMP-9 content within downstream portions of carotid plaques. In conclusion, statin treatment was associated with improvement in serum RANKL levels and reduced neutrophil activity both systemically and in atherosclerotic plaques.

Thromboxane Biosynthesis, Neutrophil and Coagulative Activation in Type IIa Hypercholesterolemia

1995 ◽  
Vol 74 (04) ◽  
pp. 1015-1019 ◽  
Author(s):  
Giovanni Davì ◽  
Antonina Ganci ◽  
Maurizio Averna ◽  
Carlo Giammarresi ◽  
Carlo Barbagallo ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Healthy Subjects ◽  
Thrombin Generation ◽  
Blood Clotting ◽  
Reductase Inhibitor ◽  
Antithrombin Iii ◽  
Atherosclerotic Plaques ◽  
Prothrombin Fragment ◽  
Cholesterol Levels ◽  
The Relationship

SummaryThromboxane (Tx) A2 biosynthesis is enhanced in the majority of patients with type IIa hypercholesterolemia. Because blood clotting activation is an important component of the inflammatory response, involved in the initiation and progression of atherosclerotic plaques, we have investigated TxA2 biosynthesis, neutrophil activation and thrombin generation in 24 patients with type IIa hypercholesterolemia.Urinary 11-dehydro-TxB2, was significantly higher (p =0.0001) in patients than in 24 sex- and age matched healthy subjects. Similarly, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complexes and plasma elastase were significantly higher in patients than incontrols. Urinary 11-dehydro-TxB2 excretion was correlated with plasma elastase (r = 0.758; p =0.000I), and prothrombin fragment 1+2 (r = 0.804; p = 0.001). The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin (20 mg/day for 2 months) significantly reduced cholesterol levels, urinary 11-dehydro-TxB2 excretion, plasma elastase and plasma Fl+2 in 8 patients.We conclude that type IIa hypercholesterolemia is associated with biochemical evidence of platelet, neutrophil and blood clotting activation. The relationship between these events remains to be investigated.

MRI-plaqueimaging detects carotid plaques with a high risk for future cerebrovascular events

2009 ◽  
Vol 36 (S 02) ◽  
Author(s):  
L Esposito ◽  
S Sadikovic ◽  
R Feurer ◽  
D Sepp ◽  
C Winkler ◽  
...  
Keyword(s):  
High Risk ◽  
Carotid Plaques ◽  
Cerebrovascular Events
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