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.

Abstract 511: Mrp8 And Mrp14,Endogenous Activators of Toll-lLke Receptor4, are Associated with Rupture-Prone Human Atherosclerotic Plaques

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mihaela G Ionita ◽  
Gerard Pasterkamp ◽  
Dominique deKleijn
Keyword(s):  
Atherosclerotic Plaque ◽  
Atherosclerotic Plaques ◽  
Atherosclerotic Lesions ◽  
Inflammatory Status ◽  
Potential Marker ◽  
Plaque Phenotype ◽  
Histological Characteristics ◽  
Unstable Plaques ◽  
Human Carotid

Objectives : Atherosclerosis is a chronic, complex inflammatory process and is the underlying cause of stroke and myocardial infarction due to rupture of the atherosclerotic plaque leading to acute occlusion of the artery in the brain or heart. Macrophages, infiltrating atherosclerotic lesions, abundantly express Mrp8 and Mrp14. Recently Mrp8, Mrp14 and the complex Mrp8/14 have been identified as endogenous ligands of Tlr-4.The role of Tlr-4 in the development and progression of the atherosclerotic plaque is well recognized and it is associated with a rupture-prone plaque phenotype. Expression of Mrps in human plaques and its relation to plaque phenotype is unknown. For this, we investigated the levels of Mrp8, Mrp14 and Mrp8/14 complex in a large number of human atherosclerotic plaques. Methods and results : Mrp8, Mrp14 and Mrp8/14 were quantified by ELISAs in human carotid endarterectomy specimens (186 patients) and plaque phenotype was determined by immunohistochemistry. Mrp levels were higher in the unstable (58 fibro-atheromatous, 64 atheromatous) compared to the stable (64 fibrous) plaques: Mrp8 p = 0.001 ; Mrp14 p = 0.001 ; Mrp8/14 p = 0.01 . Concomitantly, Mrp8, Mrp14 and Mrp8/14 were associated with characteristics of unstable plaques: more macrophages ( p = 0.024; p = 0.002; p = 0.076 ), less smooth muscle cells ( p = 0.041; p = 0.001; p = 0.074 ), larger lipid core ( p = 0.001; p = 0.001; p=0.004 ), less collagen ( p = 0.440; p = 0.011; p = 0.372 ). Furthermore, Mrp plaque levels were positively correlated with the pro-inflammatory cytokines (IL-6 and IL-8) and matrix metalloproteinsases (MMP2, MMP8 and MMP9) plaque levels. EDA, marker of stable plaques, was negatively associated with Mrps plaque levels. Histological analysis revealed that Mrps are expressed by a subgroup of plaque macrophages localized in the plaque cap and shoulder, the most rupture-prone sites of an atherosclerotic plaque. Conclusions: We show that Mrp8, Mrp14 and Mrp8/14 are strongly associated with the histological characteristics and inflammatory status of human rupture-prone plaques and identify Mrps as a potential marker for rupture-prone plaques.

Near-infrared spectroscopy

ESC CardioMed ◽  
2018 ◽  
pp. 637-640
Author(s):  
Carlo Di Mario ◽  
Carlotta Sorini Dini ◽  
Serafina Valente
Keyword(s):  
Infrared Spectroscopy ◽  
Near Infrared Spectroscopy ◽  
Near Infrared ◽  
Local Treatment ◽  
Atherosclerotic Plaques ◽  
High Lipid ◽  
Coronary Syndromes ◽  
St Elevation ◽  
Unstable Plaques

Near-infrared spectroscopy (NIRS) is a new intracoronary imaging technique that detects and quantifies cholesterol-rich atherosclerotic plaques. NIRS can be combined with intravascular ultrasound to provide morphological information together with a chemogram of the atherosclerotic plaques. This technique has been used for characterization of unstable plaques, showing a nearly universal presence of high lipid content in patients with ST elevation myocardial infarction or acute coronary syndromes, for prediction of embolization risk and for assessing the effects of cholesterol-lowering therapy. The main potential advantage of NIRS is the identification of vulnerable plaques at high risk, to be targeted by local treatment and more aggressive preventive measures.

Geometrical and Morphological Assessment of Human Endarterectomy Specimens In Vitro

2013 ◽  
Author(s):  
Renate W. Boekhoven ◽  
Marcel C. M. Rutten ◽  
Marc R. H. M. van Sambeek ◽  
Frans N. van de Vosse ◽  
Richard G. P. Lopata
Keyword(s):  
Complex Geometry ◽  
Plaque Morphology ◽  
Atherosclerotic Plaques ◽  
Rupture Risk ◽  
Temporal And Spatial ◽  
Unstable Plaques ◽  
Stenotic Arteries ◽  
3D Information

Treatment of rupture-prone carotid atherosclerotic plaques, by means of endarterectomy, is only beneficial for patients with unstable plaques, which comprise only 16% of the patient population [1]. It is therefore of great interest to assess morphology, geometry and mechanical deformation of the plaque and its components, to prevent unnecessary treatment. However, due to the complex geometry of stenotic arteries, 3D information at both high temporal and spatial resolution is required. Besides, assessment of plaque morphology in vivo can still not be routinely performed. Therefore, one has to rely on in vitro methods to obtain morphology and mechanical properties, and thus rupture risk.

In Vitro Three Dimensional Imaging of Human Carotid Atherosclerotic Plaques Using Ultrasonography

2011 ◽  
Author(s):  
Renate W. Boekhoven ◽  
Marcel C. M. Rutten ◽  
Marc R. H. M. van Sambeek ◽  
Frans N. van de Vosse
Keyword(s):  
Mechanical Properties ◽  
Carotid Artery ◽  
Carotid Endarterectomy ◽  
Early Stage ◽  
Three Dimensional ◽  
Atherosclerotic Plaques ◽  
Unstable Plaques ◽  
Human Carotid ◽  
Selection Of

Ruptured atherosclerotic plaques in the carotid artery are the main cause of stroke (70–80%). To prevent it, carotid endarterectomy is the procedure of choice in patients with a recent symptomatic 70–99% stenosis. Today, the selection of candidates is based on stenosis size only. However, endarterectomy is beneficial for only 1 out of 6 patients [1], the patients with unstable plaques (Fig. 1). Knowledge of mechanical properties of different components in the atherosclerotic arteries is important, because it will allow the identification of plaque stability at an early stage.

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.

scholarly journals An investigation into the critical role of fibre orientation in the ultimate tensile strength and stiffness of human carotid plaque caps

2020 ◽  
Author(s):  
R.D. Johnston ◽  
R.T. Gaul ◽  
C. Lally
Keyword(s):  
Atherosclerotic Plaque ◽  
Critical Role ◽  
Experimental Studies ◽  
Atherosclerotic Lesion ◽  
Collagen Fibre ◽  
Atherosclerotic Plaques ◽  
Fibrous Plaque ◽  
Carotid Plaques ◽  
Risk Of Rupture ◽  
Human Carotid

AbstractThe development and subsequent rupture of atherosclerotic plaques in human carotid arteries is a major cause of ischemic stroke. Mechanical characterization of atherosclerotic plaques can aid our understanding of this rupture risk. Despite this however, experimental studies on human atherosclerotic carotid plaques, and fibrous plaque caps in particular, are very limited. This study aims to provide further insights into atherosclerotic plaque rupture by mechanically testing human fibrous plaque caps, the region of the atherosclerotic lesion most often attributed the highest risk of rupture. The results obtained highlight the variability in the ultimate tensile stress, strain and stiffness experienced in atherosclerotic plaque caps. By pre-screening all samples using small angle light scattering (SALS) to determine the dominant fibre direction in the tissue, along with supporting histological analysis, this work suggests that the collagen fibre alignment in the circumferential direction plays the most dominant role for determining plaque structural stability. The work presented in this study could provide the basis for new diagnostic approaches to be developed, which non-invasively identify carotid plaques at greatest risk of rupture.Graphical Abstract

Mechanical Characterization of Fresh Human Carotid Atherosclerotic Plaque

2009 ◽  
Author(s):  
Eoghan Maher ◽  
Arthur Creane ◽  
Sherif Sultan ◽  
Niamh Hynes ◽  
Caitríona Lally ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Mechanical Characterization ◽  
External Carotid ◽  
Atherosclerotic Plaques ◽  
Finite Element Models ◽  
Tissue Properties ◽  
Surgical Interventions ◽  
The Relationship ◽  
Human Carotid

Quantifying the properties of atherosclerotic plaques is critical to improving our understanding of the pathogenesis of the disease. Furthermore realistic tissue properties are vital in order to obtain legitimate results from finite element models of surgical interventions used to treat cardiovascular disease. The aim of this study is to determine the mechanical properties of fresh human carotid plaques immediately following removal during endarterectomy. A number of studies have reported atherosclerotic plaque properties previously [1–3], however all of these tested cadaveric tissue. This study will further investigate in-patient and inter-patient variability, the relationship between plaque properties and their clinical classification (calcified, mixed or echolucent) and the location of the sample (common, internal, external carotid).

Notice of Removal: Characterization of human carotid plaques using multi-wavelength photoacoustic imaging

2017 ◽  
Author(s):  
Mustafa Umit Arabul ◽  
Maarten Heres ◽  
Marcel Rutten ◽  
Marc van Sambeek ◽  
Frans van de Vosse ◽  
...  
Keyword(s):  
Photoacoustic Imaging ◽  
Carotid Plaques ◽  
Multi Wavelength ◽  
Human Carotid
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