Efficient computational modelling of smooth muscle orientation and function in the aorta

Author(s):  
Malte Rolf-Pissarczyk ◽  
Maximilian P. Wollner ◽  
Douglas R. Q. Pacheco ◽  
Gerhard A. Holzapfel

Understanding the mechanical effects of smooth muscle cell (SMC) contraction on the initiation and the propagation of cardiovascular diseases such as aortic dissection is critical. Framed by elastic lamellar sheets in the lamellar unit, there are SMCs in the media with a distinct radial tilt, which indicates their contribution to the radial strength. However, the mechanical effects of this type of anisotropy have not been fully discussed. Therefore, in this study, we propose a constitutive framework that models the passive and active mechanics of the aorta, taking into account the dispersed nature of the aortic constituents by applying the discrete fibre dispersion method. We suggest an isoparametric approach by evaluating various numerical integration methods and introducing a non-uniform discretization of the unit hemisphere to increase its computational efficiency. Finally, the constitutive parameters are fitted to layer-specific experimental data and initial computational results are briefly presented. The radial tilt of SMCs is also analysed, which has a noticeable influence on the mechanical behaviour of the aorta. In the absence of sufficient experimental data, the results indicate that the active contribution of SMCs has a remarkable impact on the mechanics of the healthy aorta.

2007 ◽  
Vol 292 (5) ◽  
pp. C1672-C1680 ◽  
Author(s):  
Judith Litvin ◽  
Xing Chen ◽  
Sheri Keleman ◽  
Shimei Zhu ◽  
Michael Autieri

In injured blood vessels activated vascular smooth muscle cells (VSMCs) migrate from the media to the intima, proliferate and synthesize matrix proteins. This results in occlusion of the lumen and detrimental clinical manifestations. We have identified a novel isoform of the periostin family of proteins referred to as periostin-like factor (PLF). PLF expression in VSMCs was increased following treatment with mitogenic compounds, suggesting that PLF plays a role in VSMC activation. Correspondingly, proliferation of the cells was significantly reduced with anti-PLF antibody treatment. PLF expression increased VSMC migration, an essential cellular process leading to vascular restenosis after injury. PLF protein was localized to neointimal VSMC of rat and swine balloon angioplasty injured arteries, as well as in human arteries with transplant restenosis, supporting the hypothesis that PLF is involved in VSMC activation and vascular proliferative diseases. Taken together, these data suggest a role for PLF in the regulation of vascular proliferative disease.


2020 ◽  
Vol 96 (3) ◽  
Author(s):  
Gavin J Fenske ◽  
Sudeep Ghimire ◽  
Linto Antony ◽  
Jane Christopher-Hennings ◽  
Joy Scaria

ABSTRACT Bacterial communities resident in the hindgut of pigs, have profound impacts on health and disease. Investigations into the pig microbiome have utilized either culture-dependent, or far more commonly, culture-independent techniques using next generation sequencing. We contend that a combination of both approaches generates a more coherent view of microbiome composition. In this study, we surveyed the microbiome of Tamworth breed and feral pigs through the integration high throughput culturing and shotgun metagenomics. A single culture medium was used for culturing. Selective screens were added to the media to increase culture diversity. In total, 46 distinct bacterial species were isolated from the Tamworth and feral samples. Selective screens successfully shifted the diversity of bacteria on agar plates. Tamworth pigs are highly dominated by Bacteroidetes primarily composed of the genus Prevotella whereas feral samples were more diverse with almost equal proportions of Firmicutes and Bacteroidetes. The combination of metagenomics and culture techniques facilitated a greater retrieval of annotated genes than either method alone. The single medium based pig microbiota library we report is a resource to better understand pig gut microbial ecology and function. It allows for assemblage of defined bacterial communities for studies in bioreactors or germfree animal models.


2008 ◽  
Vol 6 (32) ◽  
pp. 293-306 ◽  
Author(s):  
A Valentín ◽  
L Cardamone ◽  
S Baek ◽  
J.D Humphrey

Arteries exhibit a remarkable ability to adapt to sustained alterations in biomechanical loading, probably via mechanisms that are similarly involved in many arterial pathologies and responses to treatment. Of particular note, diverse data suggest that cell and matrix turnover within vasoaltered states enables arteries to adapt to sustained changes in blood flow and pressure. The goal herein is to show explicitly how altered smooth muscle contractility and matrix growth and remodelling work together to adapt the geometry, structure, stiffness and function of a representative basilar artery. Towards this end, we employ a continuum theory of constrained mixtures to model evolving changes in the wall, which depend on both wall shear stress-induced changes in vasoactive molecules (which alter smooth muscle proliferation and synthesis of matrix) and intramural stress-induced changes in growth factors (which alter cell and matrix turnover). Simulations show, for example, that such considerations help explain the different rates of experimentally observed adaptations to increased versus decreased flows as well as differences in rates of change in response to increased flows or pressures.


1974 ◽  
Vol 186 (1083) ◽  
pp. 99-120 ◽  

Tissue was obtained from the testes of three men, two in the age range 72-75 years (subjects A and B) and one aged 25 years (subject C). Parts of the testes were dissected to obtain samples of interstitium and tubules. The individual components and whole tissue were each incubated with equimolar concentrations of [7 α - 3 H]pregnenolone and [4- 14 C]progesterone in Krebs-Ringer bicarbonate buffer pH 7.4, at 35 °C with the addition of glucose but without cofactors. Some incubations were carried out with the substrates [4- 14 C]androstenedione and [7 α - 3 H]testosterone. The media were extracted both at various time intervals throughout the incubation for a kinetic study of the metabolic activity and after a fixed interval of time at the end of the incubations. In some incubations with whole tissue both media and tissue were extracted. Both the tubules and interstitium displayed steroid metabolic activity. Qualitatively they yielded the same range of metabolites, one series leading to the formation of testosterone (∆ 5 pathway) and the other to a variety of C 21 compounds as represented by 5 α -pregnan-3 β -ol-20-one. With similar amounts of tissue there was little difference in the yields of the main products formed by the tubules as compared with those formed by the interstitium; in incubations with [4- 14 C]androstenedione the rate of conversion to [ 14 C ]testosterone by the tubules greatly exceeded that due to the interstitium. Marked differences were found in the pattern of steroid metabolism by whole tissue as compared to the general pattern presented by the corresponding tubules and interstitium. It is concluded that the seminiferous tubules and interstitium of the human testis are both capable of steroid metabolism and hence that whole tissue incubations alone are of limited value and could give rise to misleading data. Some clinical aspects of the results are briefly discussed.


Materials ◽  
2021 ◽  
Vol 14 (2) ◽  
pp. 450
Author(s):  
Zara Moleinia ◽  
David Bahr

The current work centers on multi-scale approaches to simulate and predict metallic nano-layers’ thermomechanical responses in crystal plasticity large deformation finite element platforms. The study is divided into two major scales: nano- and homogenized levels where Cu/Nb nano-layers are designated as case studies. At the nano-scale, a size-dependent constitutive model based on entropic kinetics is developed. A deep-learning adaptive boosting technique named single layer calibration is established to acquire associated constitutive parameters through a single process applicable to a broad range of setups entirely different from those of the calibration. The model is validated through experimental data with solid agreement followed by the behavioral predictions of multiple cases regarding size, loading pattern, layer type, and geometrical combination effects for which the performances are discussed. At the homogenized scale, founded on statistical analyses of microcanonical ensembles, a homogenized crystal plasticity-based constitutive model is developed with the aim of expediting while retaining the accuracy of computational processes. Accordingly, effective constitutive functionals are realized where the associated constants are obtained via metaheuristic genetic algorithms. The model is favorably verified with nano-scale data while accelerating the computational processes by several orders of magnitude. Ultimately, a temperature-dependent homogenized constitutive model is developed where the effective constitutive functionals along with the associated constants are determined. The model is validated by experimental data with which multiple demonstrations of temperature effects are assessed and analyzed.


2021 ◽  
Vol 73 (01) ◽  
pp. 12-13
Author(s):  
Manas Pathak ◽  
Tonya Cosby ◽  
Robert K. Perrons

Artificial intelligence (AI) has captivated the imagination of science-fiction movie audiences for many years and has been used in the upstream oil and gas industry for more than a decade (Mohaghegh 2005, 2011). But few industries evolve more quickly than those from Silicon Valley, and it accordingly follows that the technology has grown and changed considerably since this discussion began. The oil and gas industry, therefore, is at a point where it would be prudent to take stock of what has been achieved with AI in the sector, to provide a sober assessment of what has delivered value and what has not among the myriad implementations made so far, and to figure out how best to leverage this technology in the future in light of these learnings. When one looks at the long arc of AI in the oil and gas industry, a few important truths emerge. First among these is the fact that not all AI is the same. There is a spectrum of technological sophistication. Hollywood and the media have always been fascinated by the idea of artificial superintelligence and general intelligence systems capable of mimicking the actions and behaviors of real people. Those kinds of systems would have the ability to learn, perceive, understand, and function in human-like ways (Joshi 2019). As alluring as these types of AI are, however, they bear little resemblance to what actually has been delivered to the upstream industry. Instead, we mostly have seen much less ambitious “narrow AI” applications that very capably handle a specific task, such as quickly digesting thousands of pages of historical reports (Kimbleton and Matson 2018), detecting potential failures in progressive cavity pumps (Jacobs 2018), predicting oil and gas exports (Windarto et al. 2017), offering improvements for reservoir models (Mohaghegh 2011), or estimating oil-recovery factors (Mahmoud et al. 2019). But let’s face it: As impressive and commendable as these applications have been, they fall far short of the ambitious vision of highly autonomous systems that are capable of thinking about things outside of the narrow range of tasks explicitly handed to them. What is more, many of these narrow AI applications have tended to be modified versions of fairly generic solutions that were originally designed for other industries and that were then usefully extended to the oil and gas industry with a modest amount of tailoring. In other words, relatively little AI has been occurring in a way that had the oil and gas sector in mind from the outset. The second important truth is that human judgment still matters. What some technology vendors have referred to as “augmented intelligence” (Kimbleton and Matson 2018), whereby AI supplements human judgment rather than sup-plants it, is not merely an alternative way of approaching AI; rather, it is coming into focus that this is probably the most sensible way forward for this technology.


2001 ◽  
Vol 114 (19) ◽  
pp. 3507-3516 ◽  
Author(s):  
Amelia K. Scaffidi ◽  
Yuben P. Moodley ◽  
Markus Weichselbaum ◽  
Philip J. Thompson ◽  
Darryl A. Knight

Myofibroblasts, characterised by high expression of α-smooth muscle actin (α-SMA), are important and transient cells in normal wound healing but are found in increased number in various pathological conditions of the lung including asthma and pulmonary fibrosis. The mechanisms that regulate the myofibroblast phenotype are unknown but are likely to involve signals from the extracellular matrix transmitted via specific integrins. Vitronectin is a glycoprotein released during inflammation and has been shown to regulate the phenotype of vascular smooth muscle cells via αv and β1 integrins. In the current study we have examined whether vitronectin influences the phenotype and function of normal human lung fibroblasts (HFL-1). Incubation of HFL-1 cells with vitronectin induced a concentration-dependent reduction in α-SMA expression. By contrast, function-blocking monoclonal antibodies to the vitronectin integrins αv, β1, αvβ3 and αvβ5 induced the expression of α-SMA and its organization into stress fibers. Expression of α-SMA induced by all function-blocking monoclonal antibodies was abrogated by inhibition of protein kinase C and phosphatidylinositol-3 kinase, but the effects of inhibition of other signalling pathways was integrin dependent. Exposure to other extracellular matrix proteins such as fibronectin, collagen or their integrins did not influence expression of α-SMA. The expression and organization of α-SMA induced by exposure to function-blocking antibodies was translated into an augmented capacity of HFL-1 cells to contract fibroblast populated collagen gels. By contrast, contraction of collagen gels following incubation with vitronectin was not significantly different to control. This study has shown that vitronectin influences the phenotype and behaviour of HFL-1 cells by downregulating the expression of α-SMA and reducing their contractile ability. By contrast, occupancy of specific integrins by function-blocking antibodies upregulated the expression of α-SMA and induced the formation of functional stress fibers capable of contracting collagen gels. These results suggest that vitronectin modulates the fibroblast-myofibroblast phenotype, implying an important role in the remodelling process during lung development or response to injury.


Peptides ◽  
2019 ◽  
Vol 112 ◽  
pp. 48-55 ◽  
Author(s):  
Alexander T. May ◽  
Molly S. Crowe ◽  
Bryan A. Blakeney ◽  
Sunila Mahavadi ◽  
Hongxia Wang ◽  
...  

1992 ◽  
Vol 70 (4) ◽  
pp. 481-490 ◽  
Author(s):  
R. E. Garfield ◽  
G. Thilander ◽  
M. G. Blennerhassett ◽  
N. Sakai

Earlier, it was questioned whether gap junctions (GJs) were necessary for cell–cell communication in smooth muscle, and GJs were not seen in some smooth muscles. We reexamined this question in the myometrium and in intestinal smooth muscle, in light of current knowledge of the presence and function of GJs. In the uterus, numerous studies show that an increase in GJ number is associated with the onset of delivery and is required for effective parturition. In all cases, this increase in GJ number and the changes in uterine contractility were correlated with increased electrical and metabolic coupling. Evidence for the much smaller, but detectable, degree of electrical coupling in the preterm uterus is explained by the small (but again detectable) number of GJs present. In the intestine, GJs are readily detected in the circular muscle layer but have not been described in the adjacent longitudinal layer. While our immunohistochemical studies failed to detect GJs in the longitudinal layer, this may not be adequate to prove their absence. Therefore, current knowledge of GJ number and function is adequate to explain cell–cell coupling in the uterus. Although it remains uncertain whether GJs are absent from the longitudinal muscle of the intestine, there is no definitive evidence that cell–cell coupling can occur by means other than GJs.Key words: gap junctions, myometrium, connexins, smooth muscle, cell communication.


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