Arterial Wall Tissue Research Articles

Structurally Motivated Models of the Arterial Wall Tissue

Mechanical characteristics of soft biological tissues mostly depend on their hierarchy at different scales from nano- to macro-structure. It is shown that arterial wall tissue is highly sensitive to its mechanical environment and any alteration in mechanical factors such as blood pressure, triggers physio- pathological processes within arterial wall. Quantification of these mechanical properties will provide us with deeper insights of ongoing biological events. In this context, mechanical contributions of wall constituents in health and diseases are of growing interest. Hence, this review is concerned with mechanical models of arterial wall tissue with a focus on microstructurally motivated representations.

Treatment of Arterial Lesions in Drug Addicts

Arterial complications among drug addicts are rare. Their appearance can engage the vital prognosis of the patient and present a major risk of amputation. The injection of products with high cellular toxicity induces septic necrosis of the arterial wall and adjacent tissues. It is frequently responsible for acute hemorrhage. The data in the literature concerning surgical treatment are discussed. The goal of our study was to analyze the immediate and midterm results of the surgical management of these arterial lesions. Between January 2005 and April 2012, 31 drug addicts (4 women; 31.4±7.2years) presenting with 33 arterial lesions were treated. They presented with a humeral (n=15), femoral (n=13), or axillar (n=3) false aneurysm. Two patients had an arterial thrombosis. The clinical manifestations were an acute hemorrhage (n=16), a septic syndrome (n=7), a pulsatile mass (n=6), and an acute ischemia (n=4). In situ revascularization was carried out in 20 cases, in 15 patients with a bypass (9 venous and 6 prosthetic), in 2 with a venous patch, in 2 by direct suture, and in 1 by transposition of the superficial femoral artery in the deep femoral artery. Extra-anatomic bypass revascularization was performed in 6 cases (4 venous and 2 prosthetic). The other techniques used were ligature (n=5) and medical care (n=2). Two patients had an additional procedure with a musculocutaneous epigastric pedicled flap in order to fill the loss of substance. The early rate of reinterventions was 38.7% at 30days (12 patients), because of a suture line hemorrhage related to sepsis (n=6), a bypass thrombosis (n=5), and of acute ischemia after a arterial ligature. These complications occurred mainly on extremities, having had an anatomic revascularization (n=9). Six extra-anatomic revascularizations had to be performed in second intention. The average follow-up was 8.6months (range: 1-73.5months), and 15 patients were lost to follow-up at 6months. The patients were followed by duplex ultrasonography and/or angioscanner. Primary and secondary actuarial patencies at 1, 3, and 6months were 61%, 46%, 46%, and 91%, 81%, and 71%, respectively. The rate of salvage of extremities was 100%. Our study reveals the difficulty of the management of these arterial lesions. The local and general septic process is primarily responsible for early complications. Arterial restoration with extra-anatomic bypass makes it possible to be distant from the infection. This technique can be associated with a covering flap.

Computational modelling of bulging of inflated cylindrical shells applicable to aneurysm formation and propagation in arterial wall tissue

In this paper we use a numerical procedure to analyse bifurcation and postbifurcation of inflated hyperelastic thick-walled cylinders based on the modified Riks method. In particular, the bulging mode of bifurcation is exploited in the context of aneurysm formation with cylindrical geometry in cardiovascular diseases. We focus here on orthotropic materials with two preferred directions which are mechanically equivalent and are symmetrically disposed. Arterial wall tissue is modeled with this class of constitutive equation showing significant stiffening behaviour. The onset of bulging is considered to give aneurysm formation. Analytical solutions can be found in the literature for very particular conditions involving specific material models and loads applied as well as, usually, a perfect geometry. Here, we provide a unified approach to both the prediction of bifurcation and postbifurcation propagation that can be applied to more general conditions. Furthermore, we show that bulging instability under the conditions at hand propagates axially in agreement with the propagation of aneurysms in arterial wall tissue.

Towards a role of interleukin-32 in atherosclerosis

BackgroundIL-32 has been previously shown to promote inflammation in rheumatoid arthritis patients and to contribute to IL-1β-induced ICAM-1 as well as other proinflammatory cytokines synthesis in human umbilical endothelial cells (HUVECs). Given the high rate of atherosclerosis in RA, these observations suggest that IL-32 may be involved in the inflammatory pathways of atherosclerosis. MethodsmRNA and protein levels of IL-32 were determined in human atherosclerotic arterial vessel wall tissue by quantitative real-time PCR and immunohistochemistry. HUVEC and M1/M2 macrophages were stimulated with proinflammatory cytokines and TLR ligands to assess IL-32 mRNA induction. Human THP1 macrophages were transduced with AdIL-32γ, to investigate induction of several proatherosclerotic mediators. Finally, aortas from IL-32γ transgenic mice were studied and compared with aortas from age-matched wild-type mice. ResultsIL-32 expression was detectable in human atherosclerotic arterial vessel wall, with the expression of IL-32β and IL-32γ mRNA significantly enhanced. TLR3-ligand Poly I:C in combination with IFNγ were the most potent inducers of IL-32 mRNA expression in both HUVEC and M1/M2 macrophages. Adenoviral overexpression of IL-32γ in human THP1 macrophages resulted in increased production of CCL2, sVCAM-1, MMP1, MMP9, and MMP13. The IL-32γ transgenic mice chow a normal fat diet exhibited vascular abnormalities resembling atherosclerosis. ConclusionsIL-32 acts as a proinflammatory factor and may be implicated in the inflammatory cascade contributing to atherosclerosis. By promoting the synthesis of matrix metalloproteinases, it may further contribute to plaque instability. Further studies are warranted to investigate whether IL-32 may serve as a potential therapeutic target in fighting atherosclerosis.

The vascular endothelium in diabetes and its potential as a therapeutic target

The vascular endothelium in diabetes and its potential as a therapeutic target

Numerical simulation of blood flow in a flexible stenosed abdominal real aorta

This study concerns an evaluation of pulsatile flow and arterial wall behavior in a real world model of a stenosed abdominal aorta and iliac arteries. Two different geometries of a healthy and severly stenosed abdominal aorta, extracted from CT scan images and simulations of fluid flow and tissue interaction (Fluid Solid Interaction), are carried out. The blood is taken as incompressible, non-Newtonian, and the arterial wall tissue is treated as isotropic, elastic material with uniform mechanical properties. The results of using two models with rigid and flexible walls are presented and compared. The computed pressure at the abdominal aorta for a flexible healthy wall is consistent with measured values in vivo conditions. Results show that the computed pressure is lower by 15% for the flexible model, as compared to the rigid and complaint models. Although results obtained from the FSI study of pulsatile healthy and stenosed models show a similar trend for Wall Shear Stress (WSS) patterns, considerable differences in magnitude exist. It is shown that for the cases presented here, the effects of wall flexibility and actual stenosed geometry on the flow performance of veins are noticeable.

Musashi-1 expression in atherosclerotic arteries and its relevance to the origin of arterial smooth muscle cells: Histopathological findings and speculations

The origin of smooth muscle cells in developing atherosclerotic lesions is a controversial topic with accumulating evidence indicating that at least some arterial smooth muscle cells might originate from bone marrow-derived smooth muscle cell precursors circulating in the blood. The stem cell markers currently used for the identification of stem cells in the arterial intima can be expressed by a number of different cell types residing in the arterial wall, such as mast cells, endothelial cells and dendritic cells, which can make interpretation of the data obtained somewhat ambiguous. In the present study we examined whether the putative intestinal stem cell marker Musashi-1 is expressed in the arterial wall. Using a multiplexed tandem polymerase chain reaction method (MT-PCR) and immunohistochemistry, Musashi-1 expression was revealed in human coronary arterial wall tissue segments, and this finding was followed by the demonstration of significantly higher expression levels of Musashi-1 in atherosclerotic plaques compared with those in undiseased intimal sites. Double immunohistochemistry demonstrated that in the arterial wall Musashi-1 positive cells either did not display any specific markers of cells that are known to reside in the arterial intima or Musashi-1 was co-expressed by smooth muscle α-actin positive cells. Some Musashi-1 positive cells were found along the luminal surface of arteries as well as within microvessels formed in atherosclerotic plaques by neovascularization, which supports the possibility that Musashi-1 positive cells might intrude into the arterial wall from the blood and might even represent circulating smooth muscle cell precursors.

Numerical study of oxygen transport in a carotid bifurcation

This study investigates the oxygen mass transport in the region around the human carotid bifurcation, particularly addressing the effects of bifurcation geometry and pulsatile blood flow on the oxygen transport between the blood flow and artery wall tissue, coupled with the metabolic oxygen consumption and oxygen diffusion in the artery wall tissue. The temporal variations and spatial distributions of the oxygen tension are predicted quantitatively using a geometric model of the human carotid bifurcation and realistic blood flow waveforms. Results reveal that the flow separation at the outside wall of the sinus of the internal carotid artery (ICA) can markedly alter the flow pattern, oxygen tension and the oxygen wall flux. Results also clarify that the flow unsteadiness has a secondary effect on the oxygen tension inside the wall. The non-dimensional oxygen flux, the Sherwood number Sh, at the outside wall of the ICA sinus, takes markedly lower values of about 45 than at other sites because the rates of oxygen transport by the convective flow are reduced at the outside wall of the ICA sinus. The transverse distributions of the oxygen tension inside the artery wall show parabolic profiles having minima in the middle of the wall thickness, with the lowest value of 35 mmHg. These predicted distributions of the oxygen tension inside the wall closely resemble those obtained from experiments. The results demonstrate that hypoxic zones appear inside the artery walls at locations where atherosclerotic lesions are prone to develop.

Apoprotein E as a lipid transport and signaling protein in the blood, liver, and artery wall

Apoprotein E (apoE) is synthesized by a number of tissues including the liver, brain, adipose tissue, and artery wall. The majority of apoE is found in the plasma associated with specific lipoprotein subclasses and is derived primarily from the liver. However the fact that apoE expression is sustained in nonhepatic tissues suggests that the local production must have some unique functional attribute. ApoE is involved in many steps in lipid and lipoprotein homeostasis, for the triglyceride-rich lipoproteins and for HDL. ApoE is also important for lipid homeostasis in the brain, artery wall, and adipose tissue through its synthesis by glial cells, adipocytes, and macrophages. In addition, nonlipid related functions have also been attributed to apoE, including effects on immune response and inflammation, oxidation, and smooth muscle proliferation and migration. Some of these effects have been shown to be dependent upon different domains of the protein, different concentrations, and lipidation state. Thus, this multifunctional protein impacts normal and pathophysiology at multiple levels.

The mechanisms of hyperphosphatemia-induced vascular calcification

Extensive calcification of the arterial wall and soft tissues is a frequent feature of patients with end-stage chronic kidney disease (CKD stage 5). Hyperphosphatemia and secondary hyperparathyroidism have been extensively investigated as inducing factors in cardiovascular calcification. In fact, cardiovascular disease in renal failure is associated with bone metabolism alterations. Together with passive deposition of calcium-phosphate in extraskeletal tissues, it has recently been demonstrated that inorganic phosphate induces arterial calcification directly through a real "ossification" of the tunica media in the vasculature of CKD patients. Therefore, control of serum phosphate in CKD patients becomes crucial in preventing increases in calcium x phosphate product, secondary hyperparathyroidism, and ultimately vascular calcification.

Effect of Extracellular Matrix Elements on the Transport of Paclitaxel through an Arterial Wall Tissue Mimic

Paclitaxel (PTx) is reported to have an nonuniform steady-state concentration profile in the arterial wall. We utilized epifluorescence microscopy to make precise measurements of fluorescently-labeled PTx (F-PTx) distribution through an in vitro tissue mimic which contained varying concentrations of fibrin, elastin, soybean oil, palmitic acid, and solid glass beads. As little as 0.5 mg/mL of elastin in agarose produced a 50% drop in the measured diffusion coefficient, while as much as 10 mg/mL of fibrin in agarose was required for the same reduction in rate of transport. Because no reduction in the measured diffusion coefficient was observed for solubilized, extracted elastin or unassembled elastin-like polypeptides, the effect was specific to elastic fibers that closely resembled the native elastin network. Collectively, this work identifies a potential source for the high degree of partitioning observed for PTx in native tissue and further develops an in vitro technique for exploring complex tissue-drug interactions.

Force-Induced Polarized Mitosis of Endothelial and Smooth Muscle Cells in Arterial Remodeling

Arteries display highly directional growth and remodeling that are specific to increases in the mechanical loads imposed on them by blood pressure, blood flow, and lengthwise tensile forces that are transmitted from the tissues to which they are attached. This study examined the effect of mechanical forces on the direction in which mitosis delivers daughter cells, as a mechanism for directional growth. Lateral forces were imposed on surface integrins of cultured endothelial cells by seeding the cells with arginine-glycine-aspartate peptide-coated magnetic microspheres and applying a magnetic field. Video images revealed that the mitotic axis of dividing cells became highly biased in the direction of applied force. Distribution of cortactin, which participates in polarized mitoses driven by other stimuli, was highly sensitive to mechanical loading and interfering with cortactin function arrested cell growth. Smooth muscle cell mitoses also proved to be sensitive to mechanical force: when lengthwise force imposed on rabbit carotid arteries was altered by excision of a vessel segment and reanastomosis of the cut ends, direction of mitosis was dramatically altered. These findings indicate that influences of mechanical force can modulate the manner in which mitosis of vascular cells contributes to reorganization of arterial wall tissue.

STUDY THE DEFICIENCY OF POTASSIUM, MANGANESE, COPPER AND ZINC CONCENTRATION IN THE ABDOMINAL AORTIC ANEURISM BY PIXE ANALYSIS

The concentration of some trace elements especially potassium calcium, manganese, copper and zinc in the arterial wall tissue for the aneurism patients was studied by PIXE (Proton Induced X-Ray Emission) analysis. Comparing the results with normal aortic wall tissues has been done. All the patients are in the age range of 40-60 years. The samples are derived from 15 patients by surgical operation. The results show the absence of manganese, and decreasing of potassium, Copper and Zinc in the aneurismal tissues. Change in copper concentration in the arterial wall is important in the breakdown of the elastic layer in the aneurism. Elevation of the Calcium and Iron in the aneurism tissues are obtained in the comparison with the control groups. Deficiency or elevation of some elements in the aneurism aorta can be encountered as an indicator in the biopsy analysis.

Hyperphosphatemia and vascular calcification in chronic kidney disease

‘Over the last decade, mounting evidence has been accumulated indicating that disturbances in bone and mineral metabolism in CKD patients are associated with increased morbidity and mortality.’ Extensive calcification of the arterial wall and soft tissues is a frequent feature of patients with end-stage chronic kidney disease (CKD-5) [1]. Patients on maintenance dialysis evaluated by means of electron beam computed tomography exhibit a degree of calcification fivefold greater than age- and sex-matched individuals with established coronary artery disease but normal kidney function [2]. The presence and extent of vascular calcification (VC) is a sensitive marker of underlying atherosclerotic disease and medial calcification, and is associated with arterial stiffening, systolic hypertension, left ventricular hypertrophy and an adverse cardiovascular prognosis [3]. The great increase in prevalence and extent of VC is poorly explained by traditional

A volumetric model for growth of arterial walls with arbitrary geometry and loads

Stress and deformation in arterial wall tissue are factors which may influence significantly its response and evolution. In this work we develop models based on nonlinear elasticity and finite element numerical solutions for the mechanical behaviour and the remodelling of the soft tissue of arteries, including anisotropy induced by the presence of collagen fibres. Remodelling and growth in particular constitute important features in order to interpret stenosis and atherosclerosis. The main object of this work is to model accurately volumetric growth, induced by fluid shear stress in the intima and local wall stress in arteries with patient-specific geometry and loads. The model is implemented in a nonlinear finite element setting which may be applied to realistic 3D geometries obtained from in vivo measurements. The capabilities of this method are demonstrated in several examples. Firstly a stenotic process on an idealised geometry induced by a non-uniform shear stress distribution is considered. Following the growth of a right coronary artery from an in vivo reconstructed geometry is presented. Finally, experimental measurements for growth under hypertension for rat carotid arteries are modelled.

Flow Dynamics in Expansions Characterizing Abdominal Aorta Aneurysms

Our purpose was to identify and quantify hemodynamic factors contributing to the generation, proliferation, and rupturing of abdominal aorta aneurysms (AAAs) using a computational investigation of steady laminar and turbulent flow in AAA models. Steady laminar and turbulent flows were computed using the incompressible Navier-Stokes equations. Flow fields in symmetric shapes of different extents and degrees of expansion are presented first. Two representative cases of asymmetric AAAs are considered next: an aneurysm with an elliptic cross section and an aneurysm with preferential expansion in one direction. For symmetric aneurysms, parametric studies are presented. For asymmetric aneurysms, flow fields are computed only for high flow rates representative of systolic flow. For all cases, a recirculating flow region was found in the expanded part of the AAA. Recirculation is accompanied by a minor increase in pressure but a significant increase in wall shear stress. For cases where turbulent flow was considered, it was found that the recirculation zone diminishes but the computed wall shear stress reaches levels higher than laminar flow. The levels of wall shear stress reached in turbulent flow may cause lesions of the aneurysmal wall. The minor variation of pressure within the aneurysms with smooth expansions indicates that the structural properties of the arterial wall tissue may play a significant role for the generation and subsequent proliferation of the aneurysm. However, the high values of the wall shear stress in AAAs appear to be an important hemodynamic factor that may contribute to wall degeneration and eventual rupturing. The recirculating flow in AAAs may explain the generation of intraluminal thrombi. Furthermore, the asymmetry and complexity of the flow in asymmetric AAAs may explain the frequently observed asymmetric thrombi distribution.

Does Streptococcal Pyrogenic Exotoxin-C Trigger the Onset of Kawasaki Disease? -Association between Superantigens and Autoantibody against Vascular Smooth Muscle Cells-

I) T cell receptor (TCR) usage We investigated TCR usage and antibody responses to streptococcal pyrogenic exotoxin-C (SPE-C) in order to determine whether an association exists between SPE-C and the onset of Kawasaki disease (KD). Patients and Method Fifty-four patients with KD were studied. Analysis of TCR usage was performed by adaptor-ligation PCR and microplate hybridization assay. Serum levels of antibody against SPE-C were assessed by ELISA using purified recombinant protein. Results Forty (74.1%) of the patients with KD showed significant polyclonal activation of Vβ2- and/or Vβ-6.5-bearing T cells. In 22 of 35 paired patients with KD, serum levels of anti-SPE-C antibodies (IgM) in the convalescent phase were lower than those in the acute phase. II) Detection of autoantibodies against vascular smooth muscle cells To investigate the pathogenesis of vasculitis in KD, we tested for the presence of autoantibodies against vascular smooth muscle cells in the patients. Patients and Methods Sera from 48 patients with KD were examined for reactivity with both coronary arterial wall tissues and cultured smooth muscle cells (CSMC) derived from human coronary artery, using immunofluorescence and Western immunoblotting. Results Sera from 16 of 48 patients with KD gave positive immunoreactions with the smooth muscle cells of coronary artery with anti-human IgA antibodies. Western immunoblotting revealed positive reactions of sera from 15 of 34 and 10 of 31 patients with KD against a 70-kDa protein from CSMC with IgA and IgM antibodies, respectively. Positive immunoreactivity of sera from KD patients was detected more frequently in patients with coronary arterial lesions (CAL) than in those without CAL (p <0.05). Conclusions These results suggest that an association may exist between SPE-C and the onset of KD. In addition, autoantibody against vascular smooth muscle cells may cause systemic vasculitis in KD.

Measurement of the ultrasonic properties of human coronary arteries in vitro with a 50-MHz acoustic microscope

Ultrasonic attenuation coefficient, wave propagation speed and integrated backscatter coefficient (IBC) of human coronary arteries were measured in vitro over the -6 dB frequency bandwidth (36 to 67 MHz) of a focused ultrasound transducer (50 MHz, focal distance 5.7 mm, f/number 1.7). Corrections were made for diffraction effects. Normal and diseased coronary artery sub-samples (N = 38) were obtained from 10 individuals at autopsy. The measured mean +/- SD of the wave speed (average over the entire vessel wall thickness) was 1581.04 +/- 53.88 m/s. At 50 MHz, the average attenuation coefficient was 4.99 +/- 1.33 dB/mm with a frequency dependence term of 1.55 +/- 0.18 determined over the 36- to 67-MHz frequency range. The IBC values were: 17.42 +/- 13.02 (sr.m)-1 for thickened intima, 11.35 +/- 6.54 (sr.m)-1 for fibrotic intima, 39.93 +/- 50.95 (sr.m)-1 for plaque, 4.26 +/- 2.34 (sr.m)-1 for foam cells, 5.12 +/- 5.85 (sr.m)-1 for media and 21.26 +/- 31.77 (sr.m)-1 for adventitia layers. The IBC results indicate the possibility for ultrasound characterization of human coronary artery wall tissue layer, including the situations of diseased arteries with the presence of thickened intima, fibrotic intima and plaque. The mean IBC normalized with respect to the mean IBC of the media layer seems promising for use as a parameter to differentiate a plaque or a thickened intima from a fibrotic intima.

Detection of auto-antibodies against a 70 kDa protein derived from vascular smooth muscle cells in patients with Kawasaki disease.

The aetiology and pathogenesis of Kawasaki disease (KD) remain unknown. To investigate the pathogenesis of vasculitis in KD, we tested for the presence of auto-antibodies against a component of vascular smooth muscle cells in the sera of patients with KD. Sera from 48 patients with KD, as well as sera from 14 sick children and from 22 healthy children, were examined for reactivity to both coronary arterial wall tissues and cultured smooth muscle cells (CSMC) derived from human coronary artery, using immunofluorescence and Western immunoblot assay techniques. Sera from 16 of 48 patients with KD gave positive immunoreactions to the vascular walls of coronary artery with fluorescein isothiocyanate-labelled rabbit anti-human IgA antibodies. In Western immunoblot assays, the sera from 15 of 34 and 10 of 31 patients with KD showed positive reactions against a 70 kDa protein from CSMC with IgA and IgM antibodies, respectively. Positive immunoreactivity of sera from patients with KD, determined either by immunofluorescence studies or by Western immunoblotting, was detected more frequently ( P<0.05) and more intensely ( P<0.005) in patients with coronary arterial lesions (CAL) than in those without CAL. Positive immunoreactivity of sera was prominent before intravenous immunoglobulin therapy and decreased dramatically thereafter. these data suggest that auto-antibodies against a 70 kDa protein from vascular smooth muscle cells may cause coronary arteritis and systemic vasculitis in KD.

Biomechanics of plaque rupture: progress, problems, and new frontiers.

Plaque rupture has become identified as a critical step in the evolution of arterial plaques, especially as clinically significant events occur in critical arteries. It has become common in the past dozen years or so to consider which plaques are vulnerable, even though not yet ruptured. Thrombotic events have remained significant, but in a context where they are seen as being triggered often by plaque rupture. Weaving together considerations from structural mechanics, fluid mechanics, plaque morphology, epidemiological pathology, micromechanical measurements of arterial wall tissues, and emerging information on the complex roles of the matrix metalloproteinases, this critical review draws attention to the relative paucity of data (i) on the mechanical behavior of small test portions of arterial tissues and (ii) on the relation of plaque locations to local vessel curvature and curvature flexure. This is especially important in the epicardial arteries, where combination of biplane angiograms and intravascular ultrasound (both becoming increasingly available in digital recordings) offer opportunities for clinical investigation, allied to biomechanics, to an extent previously not possible. Improved imaging and local tissue property assessments provide related opportunities for the carotid bifurcation. The discussion includes a proposal for developing an assessment scale for plaque vulnerability.