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.

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).

scholarly journals YKL-40 Aggravates Early-Stage Atherosclerosis by Inhibiting Macrophage Apoptosis in an Aven-dependent Way

2021 ◽  
Vol 9 ◽  
Author(s):  
Wei Huan ◽  
Liu Yandong ◽  
Wang Chao ◽  
Zou Sili ◽  
Bai Jun ◽  
...  
Keyword(s):  
Early Stage ◽  
Expression Level ◽  
Atherosclerotic Plaques ◽  
Caspase 9 ◽  
Apoptosis Rate ◽  
Macrophage Apoptosis ◽  
Apoptosis Inhibitor ◽  
Human Carotid

Objective: programmed cell removal in atherosclerotic plaques plays a crucial role in retarding lesion progression. Macrophage apoptosis has a critical role in PrCR, especially in early-stage lesions. YKL-40 has been shown to be elevated as lesions develop and is closely related to macrophages. This study aimed to determine the effect of YKL-40 on regulating macrophage apoptosis and early-stage atherosclerosis progression.Research design and Methods: The correlations among the expression level of YKL-40, the area of early-stage plaque, and the macrophage apoptosis rate in plaques have been shown in human carotid atherosclerotic plaques through pathological and molecular biological detection. These results were successively confirmed in vivo (Ldlr−/- mice treated by YKL-40 recombinant protein/neutralizing antibody) and in vitro (macrophages that Ykl40 up-/down-expressed) experiments. The downstream targets were predicted by iTRAQ analysis.Results: In early-stage human carotid plaques and murine plaques, the YKL-40 expression level had a significant positive correlation with the area of the lesion and a significant negative correlation with the macrophage apoptosis rate. In vivo, the plaque area of aortic roots was significantly larger in the recomb-YKL-40 group than that in IgG group (p = 0.0247) and was significantly smaller in the anti-YKL-40 group than in the IgG group (p = 0.0067); the macrophage apoptosis rate of the plaque in aortic roots was significantly lower in the recomb-YKL-40 group than that in IgG group (p = 0.0018) and was higher in anti-YKL-40 group than that in VC group. In vitro, the activation level of caspase-9 was significantly lower in RAW264.7 with Ykl40 overexpressed than that in controls (p = 0.0054), while the expression level of Aven was significantly higher than that in controls (p = 0.0031). The apoptosis rate of RAW264.7 treated by recomb-YKL40 was significantly higher in the Aven down-regulated group than that in the control group (p < 0.001). The apoptosis inhibitor Aven was confirmed as the target molecule of YKL-40. Mechanistically, YKL-40 could inhibit macrophage apoptosis by upregulating Aven to suppress the activation of caspase-9.Conclusion: YKL-40 inhibits macrophage apoptosis by upregulating the apoptosis inhibitor Aven to suppress the activation of caspase-9, which may impede normal PrCR and promote substantial accumulation in early-stage plaques, thereby leading to the progression of atherosclerosis.

Three-Dimensional High Resolution Scaffold Fiber Architecture and Morphology in Tissue Engineered Heart Valve Tissue

2010 ◽  
Author(s):  
Chad E. Eckert ◽  
Brandon T. Mikulis ◽  
Dane Gerneke ◽  
Danielle Gottlieb ◽  
Bruce Smaill ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
High Resolution ◽  
Heart Valve ◽  
Structural Information ◽  
Three Dimensional ◽  
Tissue Scaffold ◽  
Valve Tissue ◽  
Sampling Protocols ◽  
Heart Valve Tissue

Engineered heart valve tissue (EHVT) has received much attention as a potential pediatric valve replacement therapy, offering prospective long-term functional improvements over current options. A significant gap in the literature exists, however, regarding estimating tissue mechanical properties from tissue-scaffold composites. Detailed three-dimensional structural information prior to implantation (in vitro) and after implantation in (in vivo) is needed for improved modeling of tissue properties. As such, a novel high-resolution imaging technique will be employed to obtain three-dimensional microstructural information. Analysis techniques will be used to fully quantify constituents of interest including scaffold, collagen, and cellular information and to develop appropriate two-dimensional sectioning sampling protocols. It is the intent of this work to guide modeling efforts to better elucidate EHVT tissue-specific mechanical properties.

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.

scholarly journals Improved Bioactivity of 3D Printed Porous Titanium Alloy Scaffold with Chitosan/Magnesium-Calcium Silicate Composite for Orthopaedic Applications

Materials ◽  
2019 ◽  
Vol 12 (2) ◽  
pp. 203 ◽  
Author(s):  
Chun-Hao Tsai ◽  
Chih-Hung Hung ◽  
Che-Nan Kuo ◽  
Cheng-Yu Chen ◽  
Yu-Ning Peng ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Calcium Silicate ◽  
Cell Attachment ◽  
Three Dimensional ◽  
Bone Defects ◽  
Metal Alloys ◽  
Potential Candidate ◽  
Natural Bone

Recently, cases of bone defects have been increasing incrementally. Thus, repair or replacement of bone defects is gradually becoming a huge problem for orthopaedic surgeons. Three-dimensional (3D) scaffolds have since emerged as a potential candidate for bone replacement, of which titanium (Ti) alloys are one of the most promising candidates among the metal alloys due to their low cytotoxicity and mechanical properties. However, bioactivity remains a problem for metal alloys, which can be enhanced using simple immersion techniques to coat bioactive compounds onto the surface of Ti–6Al–4V scaffolds. In our study, we fabricated magnesium-calcium silicate (Mg–CS) and chitosan (CH) compounds onto Ti–6Al–4V scaffolds. Characterization of these surface-modified scaffolds involved an assessment of physicochemical properties as well as mechanical testing. Adhesion, proliferation, and growth of human Wharton’s Jelly mesenchymal stem cells (WJMSCs) were assessed in vitro. In addition, the cell attachment morphology was examined using scanning electron microscopy to assess adhesion qualities. Osteogenic and mineralization assays were conducted to assess osteogenic expression. In conclusion, the Mg–CS/CH coated Ti–6Al–4V scaffolds were able to exhibit and retain pore sizes and their original morphologies and architectures, which significantly affected subsequent hard tissue regeneration. In addition, the surface was shown to be hydrophilic after modification and showed mechanical strength comparable to natural bone. Not only were our modified scaffolds able to match the mechanical properties of natural bone, it was also found that such modifications enhanced cellular behavior such as adhesion, proliferation, and differentiation, which led to enhanced osteogenesis and mineralization downstream. In vivo results indicated that Mg–CS/CH coated Ti–6Al–4V enhances the bone regeneration and ingrowth at the critical size bone defects of rabbits. These results indicated that the proposed Mg–CS/CH coated Ti–6Al–4V scaffolds exhibited a favorable, inducive micro-environment that could serve as a promising modification for future bone tissue engineering scaffolds.

A novel method for evaluating human carotid artery elasticity: Possible detection of early stage atherosclerosis in subjects with type 2 diabetes

2008 ◽  
Vol 196 (1) ◽  
pp. 391-397 ◽  
Author(s):  
Hisashi Okimoto ◽  
Yasushi Ishigaki ◽  
Yoshihiro Koiwa ◽  
Yoshinori Hinokio ◽  
Takehide Ogihara ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Carotid Artery ◽  
Early Stage ◽  
Novel Method ◽  
Carotid Artery Elasticity ◽  
Human Carotid
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