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.

Silencing of junctional adhesion molecule-like protein attenuates atherogenesis and enhances plaque stability in ApoE−/− mice

2019 ◽  
Vol 133 (11) ◽  
pp. 1215-1228 ◽  
Author(s):  
Yu Sun ◽  
Juan Guan ◽  
Yunfeng Hou ◽  
Fei Xue ◽  
Wei Huang ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Wound Repair ◽  
Inflammatory Responses ◽  
Atherosclerotic Lesion ◽  
Atherosclerotic Plaques ◽  
Plaque Stability ◽  
Fibrous Cap ◽  
Enhanced Expression

Abstract Background: Although junctional adhesion molecule-like protein (JAML) has recently been implicated in leukocyte recruitment during inflammation and wound repair, its role in atherosclerosis remains to be elucidated. Methods and results: First, we showed that JAML was strongly expressed in atherosclerotic plaques of cardiovascular patients. Similar results were obtained with atherosclerotic plaques of ApoE−/− mice. Co-immunofluorescence staining showed that JAML was mainly expressed in macrophages. Enhanced expression of JAML in cultured macrophages was observed following exposure of the cells to oxLDL. The functional role of JAML in atherosclerosis and macrophages function was assessed by interference of JAML with shRNA in vivo and siRNA in vitro. Silencing of JAML in mice significantly attenuated atherosclerotic lesion formation, reduced necrotic core area, increased plaque fibrous cap thickness, decreased macrophages content and inflammation. In addition, histological staining showed that JAML deficiency promoted plaques to stable phenotype. In vitro, JAML siRNA treatment lowered the expression of inflammatory cytokines in macrophages treated with oxLDL. The mechanism by which JAML mediated the inflammatory responses may be related to the ERK/NF-κB activation. Conclusions: Our results demonstrated that therapeutic drugs which antagonize the function of JAML may be a potentially effective approach to attenuate atherogenesis and enhance plaque stability.

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.

Novel Strategy of the Determination of Mechanical Properties of Human Carotid Atherosclerotic Plaques

2012 ◽  
Author(s):  
Renate W. Boekhoven ◽  
Richard G. P. Lopata ◽  
Marcel C. M. Rutten ◽  
Marc R. H. M. van Sambeek ◽  
Frans N. van de Vosse
Keyword(s):  
Mechanical Properties ◽  
Carotid Endarterectomy ◽  
Early Stage ◽  
Three Dimensions ◽  
Atherosclerotic Plaques ◽  
Ct Data ◽  
Novel Strategy ◽  
Unstable Plaques ◽  
Set Up

Carotid endarterectomy is the procedure of choice in patients with a recent symptomatic stenosis of 70–99%. Currently, the selection of candidates eligible for carotid endarterectomy is based on stenosis size only. However, the treatment is only beneficial for patients with unstable plaques, which comprises only 16% of the patient population [1]. Hence, identifying plaque stability at an early stage would permit timely intervention, while substantially reducing overtreatment of stable plaques. The objective of this study is to distinguish between stable and unstable carotid atherosclerotic plaques by determining the plaque geometry, the plaque composition and the mechanical properties of plaque components in three dimensions (3D). Mechanical properties from healthy vessels were assessed earlier by van den Broek et al. [2] using ultrasound (US) imaging. They obtained a dynamic dataset in 2D + t. When blood pressure and vessel wall movement are known, mechanical properties can be extracted from these data using a constitutive model. However, atherosclerotic plaques are mostly asymmetric, and present calcifications will cause unfavorable acoustic shadowing when using US. In this study, the focus is on the assessment of plaque geometry, from in vitro echo-CT data, overcoming the aforementioned problems. In an experimental set-up (Fig. 1) both healthy and endarterectomy specimens were mounted, and exposed to physiological intraluminal pressures. Echo-CT was used to image the arterial segments in 3D+t. Automated geometry assessment of the arterial segments will be demonstrated and validated using microCT (μCT).

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.

Differential expression of collagen- and laminin-binding integrins mediates ureteric bud and inner medullary collecting duct cell tubulogenesis

2004 ◽  
Vol 287 (4) ◽  
pp. F602-F611 ◽  
Author(s):  
Dong Chen ◽  
Richard Roberts ◽  
Martin Pohl ◽  
Sanjay Nigam ◽  
Jordan Kreidberg ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Branching Morphogenesis ◽  
Integrin Subunit ◽  
Integrin Expression ◽  
Dependent Manner ◽  
Ureteric Bud ◽  
Laminin Receptors ◽  
Temporal And Spatial

Inner medullary collecting ducts (IMCD) are terminally differentiated structures derived from the ureteric bud (UB). UB development is mediated by changes in the temporal and spatial expression of integrins and their respective ligands. We demonstrate both in vivo and in vitro that the UB expresses predominantly laminin receptors (α3β1-, α6β1-, and α6β4-integrins), whereas the IMCD expresses both collagen (α1β1- and α2β1-integrins) and laminin receptors. Cells derived from the IMCD, but not the UB, undergo tubulogenesis in collagen-I (CI) gels in an α1β1- and α2β1-dependent manner. UB cells transfected with the α2-integrin subunit undergo tubulogenesis in CI, suggesting that collagen receptors are required for branching morphogenesis in CI. In contrast, both UB and IMCD cells undergo tubulogenesis in CI/Matrigel gels. UB cells primarily utilize α3β1- and α6-integrins, whereas IMCD cells mainly employ α1β1 for this process. These results demonstrate a switch in integrin expression from primarily laminin receptors in the early UB to both collagen and laminin receptors in the mature IMCD, which has functional consequences for branching morphogenesis in three-dimensional cell culture models. This suggests that temporal and spatial changes in integrin expression could help organize the pattern of branching morphogenesis of the developing collecting system in vivo.

scholarly journals Biodistribution of Nanostructured Lipid Carriers in Mice Atherosclerotic Model

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3499 ◽  
Author(s):  
Devel ◽  
Almer ◽  
Cabella ◽  
Beau ◽  
Bernes ◽  
...  
Keyword(s):  
Colloidal Stability ◽  
Ex Vivo ◽  
Particle Diameter ◽  
Nanostructured Lipid Carriers ◽  
Atherosclerotic Plaques ◽  
Particle Uptake ◽  
Atherosclerotic Lesions ◽  
Physico Chemical

Atherosclerosis is a major cardiovascular disease worldwide, that could benefit from innovative nanomedicine imaging tools and treatments. In this perspective, we here studied, by fluorescence imaging in ApoE-/- mice, the biodistribution of non-functionalized and RXP470.1-targeted nanostructured lipid carriers (NLC) loaded with DiD dye. RXP470.1 specifically binds to MMP12, a metalloprotease that is over-expressed by macrophages residing in atherosclerotic plaques. Physico-chemical characterizations showed that RXP-NLC (about 105 RXP470.1 moieties/particle) displayed similar features as non-functionalized NLC in terms of particle diameter (about 60-65 nm), surface charge (about −5 — −10 mV), and colloidal stability. In vitro inhibition assays demonstrated that RXP-NLC conserved a selectivity and affinity profile, which favored MMP-12. In vivo data indicated that NLC and RXP-NLC presented prolonged blood circulation and accumulation in atherosclerotic lesions in a few hours. Twenty-four hours after injection, particle uptake in atherosclerotic plaques of the brachiocephalic artery was similar for both nanoparticles, as assessed by ex vivo imaging. This suggests that the RXP470.1 coating did not significantly induce an active targeting of the nanoparticles within the plaques. Overall, NLCs appeared to be very promising nanovectors to efficiently and specifically deliver imaging agents or drugs in atherosclerotic lesions, opening avenues for new nanomedicine strategies for cardiovascular diseases.

scholarly journals In vitro morphogenesis of chick embryo hypertrophic cartilage.

1987 ◽  
Vol 105 (2) ◽  
pp. 999-1006 ◽  
Author(s):  
C Tacchetti ◽  
R Quarto ◽  
L Nitsch ◽  
D J Hartmann ◽  
R Cancedda
Keyword(s):  
Chick Embryo ◽  
Type I ◽  
Cell Aggregates ◽  
In Vitro Morphogenesis ◽  
Temporal And Spatial Distribution ◽  
Hypertrophic Cartilage ◽  
Histologic Appearance ◽  
Temporal And Spatial

Dedifferentiated chick embryo chondrocytes (Castagnola, P., G. Moro, F. Descalzi-Cancedda, and R. Cancedda, 1986, J. Cell Biol., 102:2310-2317), when transferred to suspension culture on agarose-coated dishes in the presence of ascorbic acid, aggregate and remain clustered. With time in culture, clusters grow in size and adhere to each other, forming structures that may be several millimeters in dimension. These structures after 7 d of culture have the histologic appearance of mature hypertrophic cartilage partially surrounded by a layer of elongated cells resembling the perichondrium. Cells inside the aggregates have ultrastructural features of stage I (proliferating) or stage II (hypertrophic) chondrocytes depending on their location. Occurrence and distribution of type I, II, and X collagens in the in vitro-formed cartilage at different times of culture, show a temporal and spatial distribution of these antigens reminiscent of the maturation events occurring in the cartilage in vivo. A comparable histologic appearance is shown also by cell aggregates obtained starting with a population of cells derived from a single, cloned, dedifferentiated chondrocyte.

In vivo and in vitro evidence for the glycoxidation of low density lipoprotein in human atherosclerotic plaques

2000 ◽  
Vol 150 (2) ◽  
pp. 343-355 ◽  
Author(s):  
Yoshinobu Imanaga ◽  
Noriyuki Sakata ◽  
Shigeo Takebayashi ◽  
Akira Matsunaga ◽  
Jun Sasaki ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherosclerotic Plaques ◽  
Low Density

In vivo and in vitro evidence that 99mTc-HYNIC-interleukin-2 is able to detect T lymphocytes in vulnerable atherosclerotic plaques of the carotid artery

2014 ◽  
Vol 41 (9) ◽  
pp. 1710-1719 ◽  
Author(s):  
Andor W. J. M. Glaudemans ◽  
Elena Bonanno ◽  
Filippo Galli ◽  
Clark J. Zeebregts ◽  
Erik F. J. de Vries ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Carotid Artery ◽  
Interleukin 2 ◽  
Atherosclerotic Plaques

scholarly journals MicroRNAs in the Atherosclerotic Plaque

2013 ◽  
Vol 59 (12) ◽  
pp. 1708-1721 ◽  
Author(s):  
Emma Raitoharju ◽  
Niku Oksala ◽  
Terho Lehtimäki
Keyword(s):  
Atherosclerotic Plaque ◽  
Mirna Expression ◽  
Drug Targets ◽  
Human Peripheral Blood ◽  
Expression Profiles ◽  
Mirna Profile ◽  
In Vivo Studies ◽  
Atherosclerotic Plaques

BACKGROUND MicroRNAs (miRNA, miR) are noncoding RNAs that regulate gene expression by hindering translation. miRNA expression profiles have been shown to differ in vivo and in vitro in many cellular processes associated with cardiovascular diseases (CVDs). The progression of CVDs has also been shown to alter the blood miRNA profile in humans. CONTENT We summarize the results of animal and cell experiments concerning the miRNA profile in the atherosclerotic process and the changes which occur in the blood miRNA profile of individuals with CVD. We also survey the relationship of these CVD-related miRNAs and their expression in the human advanced atherosclerotic plaque, thereby providing more insight into miRNA function in human atherosclerotic lesions. The miRNAs miR-126, -134, -145, -146a, -198, -210, -340*, and -92a were found to be expressed differently in the blood of individuals affected and unaffected by CVD. These differences paralleled those seen in tissue comparisons of miRNA expression in advanced atherosclerotic plaques and healthy arteries. Furthermore, several miRNAs associated with atherosclerosis in in vitro studies (such as miR-10a, -126, -145, -146a/b, -185, -210, and -326) were expressed in plaques in a similar pattern as was predicted by the in vitro experiments. The clinical implications of miRNAs in atherosclerosis as biomarkers and as possible drug targets are also reviewed. SUMMARY miRNA profiles in in vitro and in vivo studies as well as in human peripheral blood are quite representative of the miRNA expression in human atherosclerotic plaques. miRNAs appear promising in terms of future clinical applications.

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