The failure of intracellular zinc accumulation is a key process in prostate carcinogenesis. Although prostate cancer cells can accumulate zinc after long-term exposure, chronic zinc oversupply may accelerate prostate carcinogenesis or chemoresistance. Because cancer progression is associated with energetically demanding cytoskeletal rearrangements, we investigated the effect of long-term zinc presence on biophysical parameters, ATP production, and EMT characteristics of two prostate cancer cell lines (PC-3, 22Rv1). Prolonged exposure to zinc increased ATP production, spare respiratory capacity, and induced a response in PC-3 cells, characterized by remodeling of vimentin and a shift of cell dry mass density and caveolin-1 to the perinuclear region. This zinc-induced remodeling correlated with a greater tendency to maintain actin architecture despite inhibition of actin polymerization by cytochalasin. Zinc partially restored epithelial characteristics in PC-3 cells by decreasing vimentin expression and increasing E-cadherin. Nevertheless, the expression of E-cadherin remained lower than that observed in predominantly oxidative, low-invasive 22Rv1 cells. Following long-term zinc exposure, we observed an increase in cell stiffness associated with an increased refractive index in the perinuclear region and an increased mitochondrial content. The findings of the computational simulations indicate that the mechanical response cannot be attributed exclusively to alterations in cytoskeletal composition. This observation suggests the potential involvement of an additional, as yet unidentified, mechanical contributor. These findings indicate that long-term zinc exposure alters a group of cellular parameters towards an invasive phenotype, including an increase in mitochondrial number, ATP production, and cytochalasin resistance. Ultimately, these alterations are manifested in the biomechanical properties of the cells.
- Publikační typ
- časopisecké články MeSH
The study deals with the process of estimation of material parameters from uniaxial test data of arterial tissue and focuses on the role of transverse strains. Two fitting strategies are analyzed and their impact on the predictive and descriptive capabilities of the resulting model is evaluated. The standard fitting procedure (strategy A) based on longitudinal stress-strain curves is compared with the enhanced approach (strategy B) taking also the transverse strain test data into account. The study is performed on a large set of material data adopted from literature and for a variety of constitutive models developed for fibrous soft tissues. The standard procedure (A) ignoring the transverse strain test data is found rather hazardous, leading often to unrealistic predictions of the model exhibiting auxetic behaviour. In contrast, the alternative fitting method (B) ensures a realistic strain response of the model and is proved to be superior since it does not require any significant demands of computational effort or additional testing. The results presented in this paper show that even the artificial transverse strain data (i.e., not measured during testing but generated ex post based on assumed Poisson's ratio) are much less hazardous than total disregard of the transverse strain response.
- MeSH
- arterie * MeSH
- biologické modely * MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND OBJECTIVE: Geometry of aorto-iliac bifurcation may affect pressure and wall stress in aorta and thus potentially serve as a predictor of abdominal aortic aneurysm (AAA), similarly to hypertension. METHODS: Effect of aorto-iliac bifurcation geometry was investigated via parametric analysis based on two-way weakly coupled fluid-structure interaction simulations. The arterial wall was modelled as isotropic hyperelastic monolayer, and non-Newtonian behaviour was introduced for the fluid. Realistic boundary conditions of the pulsatile blood flow were used on the basis of experiments in literature and their time shift was tailored to the pulse wave velocity in the model to obtain physiological wave shapes. Eighteen idealized and one patient-specific geometries of human aortic tree with common iliac and renal arteries were considered with different angles between abdominal aorta (AA) and both iliac arteries and different area ratios (AR) of iliac and aortic luminal cross sections. RESULTS: Peak wall stress (PWS) and systolic blood pressure (SBP) were insensitive to the aorto-iliac angles but sensitive to the AR: when AR decreased by 50%, the PWS and SBP increased by up to 18.4% and 18.8%, respectively. CONCLUSIONS: Lower AR (as a result of the iliac stenosis or aging), rather than the aorto-iliac angles increases the BP in the AA and may be thus a risk factor for the AAA development.
A novel method for semiautomated assessment of directions of collagen fibers in soft tissues using histological image analysis is presented. It is based on multiple rotated images obtained via polarized light microscopy without any additional components, i.e., with just two polarizers being either perpendicular or nonperpendicular (rotated). This arrangement breaks the limitation of 90° periodicity of polarized light intensity and evaluates the in-plane fiber orientation over the whole 180° range accurately and quickly. After having verified the method, we used histological specimens of porcine Achilles tendon and aorta to validate the proposed algorithm and to lower the number of rotated images needed for evaluation. Our algorithm is capable to analyze 5·105 pixels in one micrograph in a few seconds and is thus a powerful and cheap tool promising a broad application in detection of collagen fiber distribution in soft tissues.
- MeSH
- Achillova šlacha metabolismus MeSH
- algoritmy MeSH
- extracelulární matrix metabolismus MeSH
- kolagen metabolismus MeSH
- mikroskopie metody MeSH
- optické zobrazování metody MeSH
- počítačové zpracování obrazu metody MeSH
- polarizační mikroskopie metody MeSH
- prasata MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Biomechanical rupture risk assessment of abdominal aortic aneurysm (AAA) requires information about failure properties of aneurysmal tissue. There are large differences between reported values. Among others, studies vary in using either axially or circumferentially oriented samples. This study investigates the effect of sample orientation on failure properties. METHODS: Aneurysmal tissues from 45 patients (11 females) were harvested during open AAA repair, cut into uniaxial samples (90) and tested mechanically within 3 h. If possible, the samples were cut in both axial (49 samples) and circumferential (41 samples) directions. Wall thickness, First Piola-Kirchhoff strength Pult and ultimate tension Tult were recorded. Influence of sample orientation and other clinical parameters were investigated using non parametric tests. RESULTS: Medians of Pult (values 1100 kPa for circumferential vs. 715 kPa for axial direction, p < 10-4) and Tult (17.4 N/cm in circumferential vs. 11.2 N/cm in axial direction, p < 10-4) were significantly higher in circumferential direction. For paired data, the median of difference was 411 kPa (p < 10-3) in Pult and 7.4 N/cm (p < 10-4) in Tult in favor of circumferential direction. CONCLUSIONS: In this first study of anisotropy in AAA wall failure properties using paired comparisons, the strength in circumferential orientation was found to be higher than in axial orientation.
- MeSH
- aneurysma břišní aorty * MeSH
- anizotropie MeSH
- biomechanika MeSH
- hodnocení rizik MeSH
- lidé MeSH
- mechanický stres MeSH
- ruptura aorty * MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The paper deals with the impact of chosen geometric and material factors on maximal stresses in carotid atherosclerotic plaque calculated using patient-specific finite element models. These stresses are believed to be decisive for the plaque vulnerability but all applied models suffer from inaccuracy of input data, especially when obtained in vivo only. One hundred computational models based on ex vivo MRI are used to investigate the impact of wall thickness, MRI slice thickness, lipid core and fibrous tissue stiffness, and media anisotropy on the calculated peak plaque and peak cap stresses. The investigated factors are taken as continuous in the range based on published experimental results, only the impact of anisotropy is evaluated by comparison with a corresponding isotropic model. Design of Experiment concept is applied to assess the statistical significance of these investigated factors representing uncertainties in the input data of the model. The results show that consideration of realistic properties of arterial wall in the model is decisive for the stress evaluation; assignment of properties of fibrous tissue even to media and adventitia layers as done in some studies may induce up to eightfold overestimation of peak stress. The impact of MRI slice thickness may play a key role when local thin fibrous cap is present. Anisotropy of media layer is insignificant, and the stiffness of fibrous tissue and lipid core may become significant in some combinations.
- MeSH
- analýza metodou konečných prvků MeSH
- arteriae carotides diagnostické zobrazování patologie MeSH
- aterosklerotický plát diagnostické zobrazování patologie MeSH
- biomechanika MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mechanické jevy * MeSH
- modely kardiovaskulární MeSH
- počítačové modelování podle konkrétního pacienta * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: Several studies of biomechanical rupture risk assessment (BRRA) showed its advantage over the diameter criterion in rupture risk assessment of abdominal aortic aneurysm (AAA). However, BRRA studies have not investigated the predictability of biomechanical risk indices at different time points ahead of rupture, nor have they been performed blinded for biomechanical analysts. The objective of this study was to test the predictability of the BRRA method against diameter-based risk indices in a quasi-prospective patient cohort study. METHODS: In total, 12 women and 31 men with intact AAAs at baseline have been selected retrospectively at two medical centers. Within 56 months, 19 cases ruptured, whereas 24 cases remained intact within 2 to 56 months. This outcome was kept confidential until all biomechanical activities in this study were finished. The biomechanical AAA rupture risk was calculated at baseline using high-fidelity and low-fidelity finite element method models. The capability of biomechanics-based and diameter-based risk indices to predict the known outcomes at 1 month, 3 months, 6 months, 9 months, and 12 months after baseline was validated. Besides common cohort statistics, the area under the curve (AUC) of receiver operating characteristic curves has been used to grade the different rupture risk indices. RESULTS: Up to 9 months ahead of rupture, the receiver operating characteristic analysis of biomechanics-based risk indices showed a higher AUC than diameter-based indices. Six months ahead of rupture, the largest difference was observed with an AUC of 0.878 for the high-fidelity biomechanical risk index, 0.859 for the low-fidelity biomechanical risk index, 0.789 for the diameter, and 0.821 for the sex-adjusted diameter. In predictions beyond 9 months, none of the risk indices proved to be superior. CONCLUSIONS: High-fidelity biomechanical modeling improves the predictability of AAA rupture. Asymptomatic AAA patients with high biomechanical AAA rupture risk indices have an increased risk of rupture. Integrating biomechanics-based diagnostic indices may significantly decrease the false-positive rate in AAA treatment. CLINICAL RELEVANCE: Rupture of abdominal aortic aneurysm (AAA) is the tenth leading cause of death in men older than 60 years; however, the currently used maximal diameter criterion has a high false-positive rate. In this study, we have compared this criterion with biomechanical rupture risk assessment on the unique data set of 43 asymptomatic AAAs, of which 19 ruptured later. Moreover, the AAA outcome was blinded to the operator for the first time. Our data demonstrated that the biomechanical rupture risk assessment is superior to maximal diameter in predicting AAA rupture up to 9 months ahead and significantly decreases the false-positive rate.
- MeSH
- aneurysma břišní aorty diagnóza epidemiologie patofyziologie MeSH
- asymptomatické nemoci MeSH
- biomechanika MeSH
- hodnocení rizik metody MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- prediktivní hodnota testů MeSH
- retrospektivní studie MeSH
- ruptura aorty diagnóza epidemiologie patofyziologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
This study investigates the impact of reduced transmural conduction velocity (TCV) on output parameters of the human heart. In a healthy heart, the TCV contributes to synchronization of the onset of contraction in individual layers of the left ventricle (LV). However, it is unclear whether the clinically observed decrease of TCV contributes significantly to a reduction of LV contractility. The applied three-dimensional finite element model of isovolumic contraction of the human LV incorporates transmural gradients in electromechanical delay and myocyte shortening velocity and evaluates the impact of TCV reduction on pressure rise (namely, (dP/dt)max) and on isovolumic contraction duration (IVCD) in a healthy LV. The model outputs are further exploited in the lumped "Windkessel" model of the human cardiovascular system (based on electrohydrodynamic analogy of respective differential equations) to simulate the impact of changes of (dP/dt)max and IVCD on chosen systemic parameters (ejection fraction, LV power, cardiac output, and blood pressure). The simulations have shown that a 50% decrease in TCV prolongs substantially the isovolumic contraction, decelerates slightly the LV pressure rise, increases the LV energy consumption, and reduces the LV power. These negative effects increase progressively with further reduction of TCV. In conclusion, these results suggest that the pumping efficacy of the human LV decreases with lower TCV due to a higher energy consumption and lower LV power. Although the changes induced by the clinically relevant reduction of TCV are not critical for a healthy heart, they may represent an important factor limiting the heart function under disease conditions.
- MeSH
- fibrilace síní patofyziologie MeSH
- hemodynamika fyziologie MeSH
- lidé MeSH
- modely kardiovaskulární * MeSH
- počítačová simulace * MeSH
- převodní systém srdeční fyziologie MeSH
- srdce - funkce komor fyziologie MeSH
- srdeční komory patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Volumetric compressibility and Poisson's ratios of fibrous soft tissues are analyzed in this paper on the basis of constitutive models and experimental data. The paper extends the previous work of Skacel and Bursa (J Mech Behav Biomed Mater, 54, pp. 316-327, 2016), dealing with incompressible behaviour of constitutive models, to the area of compressibility. Both recent approaches to structure-based constitutive modelling of anisotropic fibrous biomaterials (based on either generalized structure tensor or angular integration) are analyzed, including their compressibility-related aspects. New experimental data related to compressibility of porcine arterial layer are presented and compared with the theoretical predictions of analyzed constitutive models. The paper points out the drawbacks of recent models with distributed fibres orientation since none of the analyzed constitutive models seems to be capable to predict the experimentally observed Poisson's ratios and volume change satisfactory.
- MeSH
- arterie * MeSH
- biologické modely * MeSH
- biomechanika MeSH
- mechanický stres MeSH
- pevnost v tlaku * MeSH
- prasata MeSH
- testování materiálů * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Peak stress in the fibrous cap of atherosclerotic plaque is largely determined by the cap thickness which cannot be accurately estimated in vivo. This parametric study investigates idealized atherosclerotic plaque geometries. Finite element modeling is applied to search for larger morphological features associated with high cap stresses. By varying seven geometrical and two loading parameters, 100 3D model geometries of atherosclerotic plaques in common iliac artery were generated. In each model peak cap stress was calculated, and statistical comparison of the geometries generating the highest and lowest peak cap stresses was performed. The analysis showed that, compared to geometries generating the lowest stresses, those with high peak cap stress had a significantly lower cap thickness, higher stenosis ratio, lower relative lipid core volume, and cap shoulder radius larger than lipid core radius. High cap stress was observed for cap thicknesses up to 0.13 mm. It can be concluded that vulnerable plaques contain thin fibrous cap, large stenosis ratio and only moderate small-radius lipid core which reaches the shoulder region of the fibrous cap.
