scholarly journals Contractile Smooth Muscle and Active Stress Generation in Porcine Common Carotids

2017 ◽  
Vol 140 (1) ◽  
Author(s):  
Boran Zhou ◽  
David A. Prim ◽  
Eva J. Romito ◽  
Liam P. McNamara ◽  
Francis G. Spinale ◽  
...  

The mechanical response of intact blood vessels to applied loads can be delineated into passive and active components using an isometric decomposition approach. Whereas the passive response is due predominantly to the extracellular matrix (ECM) proteins and amorphous ground substance, the active response depends on the presence of smooth muscle cells (SMCs) and the contractile machinery activated within those cells. To better understand determinants of active stress generation within the vascular wall, we subjected porcine common carotid arteries (CCAs) to biaxial inflation–extension testing under maximally contracted or passive SMC conditions and semiquantitatively measured two known markers of the contractile SMC phenotype: smoothelin and smooth muscle-myosin heavy chain (SM-MHC). Using isometric decomposition and established constitutive models, an intuitive but novel correlation between the magnitude of active stress generation and the relative abundance of smoothelin and SM-MHC emerged. Our results reiterate the importance of stretch-dependent active stress generation to the total mechanical response. Overall these findings can be used to decouple the mechanical contribution of SMCs from the ECM and is therefore a powerful tool in the analysis of disease states and potential therapies where both constituent are altered.

Author(s):  
Rana Rezakhaniha ◽  
Nikos Stergiopulos

Constitutive equations reflecting well the microstructure are fundamental for the detailed stress analysis of the arterial tissue. Vascular tissue is an inhomogeneous and incompressible material which undergoes large deformations and shows highly anisotropic nonlinear behavior. These properties make strain energy functions (SEFs) a suitable tool to derive constitutive equations. Structural constitutive models try to integrate the histological and morphological characteristics of the tissue by introducing parameters with physical meaning, such as the fraction of each wall constituent, the elastic properties of single elastin or collagen fibers or the angle of collagen fibers.


Author(s):  
Michael J. McClure ◽  
Scott A. Sell ◽  
David G. Simpson ◽  
Beat H. Walpoth ◽  
Gary L. Bowlin

The architecture of the vascular wall is highly intricate and requires unique biomechanical properties in order to function properly. Native artery is composed of a mix of collagen, elastin, endothelial cells (ECs), smooth muscle cells (SMC), fibroblasts, and proteoglycans arranged into three distinct layers: the intima, media, and adventitia. Throughout artery, collagen and elastin play an important role, providing a mechanical backbone, preventing vessel rupture, and promoting recovery while undergoing pulsatile deformations [1]. The low-strain mechanical response of artery to blood flow is dominated by the elastic behavior of elastin which prevents pulsatile energy from being dissipated as heat [2]. Previous work has shown the ability to fabricate multi-layered electrospun scaffolds composed of polycaprolactone (PCL), elastin (ELAS), and collagen (COL), and their associated mechanical advantages. PCL was chosen, in this case, to provide mechanical integrity and elasticity, while elastin and collagen would provide further elasticity and bioactivity [3,4]. However, when the grafts were implanted in the descending aorta of a rat, cellular results were not as desirable as predicted. Therefore, further graft optimization was required. The hypothesis of this study was that blended polymers and biopolymers would be conducive for cellular attachment through specific integrin binding sites. To test this hypothesis, human umbilical artery smooth muscle cells (hUASMC) were seeded on electrospun PCL, COL, and ELAS blends for evaluation in a cell adhesion inhibition experiment.


2007 ◽  
Vol 85 (7) ◽  
pp. 715-726 ◽  
Author(s):  
Pasquale Chitano ◽  
Lu Wang ◽  
Thomas M. Murphy

Evidence for contributions of airway smooth muscle (ASM) to the hyperresponsiveness of newborn and juvenile airways continues to accumulate. In our laboratory, 3 novel paradigms of hyperresponsiveness of newborn and young ASM have recently emerged using a guinea pig model of maturation in 3 age groups: 1 week (newborn), 3 weeks (juvenile), and 2–3 months (adult). The first paradigm includes evidence for a natural decline after newborn and juvenile life of the velocity of ASM shortening associated with a decrease in regulatory myosin light chain phosphorylation and a parallel decline in the content of myosin light chain kinase. Associated with the decrease in ASM shortening with age is an increase in the internal resistance to shortening. Dynamic stiffness is shown to relate inversely to the expression of myosin light chain kinase. This suggests that developmental changes in shortening relate inversely to the stiffness of the ASM early in shortening, suggesting a dynamic role for the cytoskeleton in facilitating and opposing ASM shortening. This relationship can be approximated as (dP/dt)max ≈ (dP/dL)passive × (dL/dt)max (the maximal rate of increase of active stress generation ≈ to the passive stiffness × the maximal shortening velocity). The second paradigm demonstrates that newborn ASM, unlike that in adults, does not relax during prolonged electric field stimulation. The impaired relaxation is related to changes in prostanoid synthesis and acetylcholinesterase function. The third paradigm demonstrates that, whereas oscillatory strain serves to transiently relax adult ASM, in newborns it induces (after the initial relaxation) a sustained potentiation of active stress. This is related to developmental changes in the prostanoid release. Together, these paradigms demonstrate that ASM contributes by multiple mechanisms to the natural hyperresponsiveness of newborn and juvenile airways. Future studies will elaborate the mechanisms and extend these paradigms to ASM hyperresponsiveness following sensitization in early life.


Polymers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 369
Author(s):  
Xintao Fu ◽  
Zepeng Wang ◽  
Lianxiang Ma

In this paper, some representative hyperelastic constitutive models of rubber materials were reviewed from the perspectives of molecular chain network statistical mechanics and continuum mechanics. Based on the advantages of existing models, an improved constitutive model was developed, and the stress–strain relationship was derived. Uniaxial tensile tests were performed on two types of filled tire compounds at different temperatures. The physical phenomena related to rubber deformation were analyzed, and the temperature dependence of the mechanical behavior of filled rubber in a larger deformation range (150% strain) was revealed from multiple angles. Based on the experimental data, the ability of several models to describe the stress–strain mechanical response of carbon black filled compound was studied, and the application limitations of some constitutive models were revealed. Combined with the experimental data, the ability of Yeoh model, Ogden model (n = 3), and improved eight-chain model to characterize the temperature dependence was studied, and the laws of temperature dependence of their parameters were revealed. By fitting the uniaxial tensile test data and comparing it with the Yeoh model, the improved eight-chain model was proved to have a better ability to predict the hyperelastic behavior of rubber materials under different deformation states. Finally, the improved eight-chain model was successfully applied to finite element analysis (FEA) and compared with the experimental data. It was found that the improved eight-chain model can accurately describe the stress–strain characteristics of filled rubber.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1485
Author(s):  
Adrian Sowka ◽  
Pawel Dobrzyn

Studies of adipose tissue biology have demonstrated that adipose tissue should be considered as both passive, energy-storing tissue and an endocrine organ because of the secretion of adipose-specific factors, called adipokines. Adiponectin is a well-described homeostatic adipokine with metabolic properties. It regulates whole-body energy status through the induction of fatty acid oxidation and glucose uptake. Adiponectin also has anti-inflammatory and antidiabetic properties, making it an interesting subject of biomedical studies. Perivascular adipose tissue (PVAT) is a fat depot that is conterminous to the vascular wall and acts on it in a paracrine manner through adipokine secretion. PVAT-derived adiponectin can act on the vascular wall through endothelial cells and vascular smooth muscle cells. The present review describes adiponectin’s structure, receptors, and main signaling pathways. We further discuss recent studies of the extent and nature of crosstalk between PVAT-derived adiponectin and endothelial cells, vascular smooth muscle cells, and atherosclerotic plaques. Furthermore, we argue whether adiponectin and its receptors may be considered putative therapeutic targets.


Author(s):  
Aref Ghaderi ◽  
Vahid Morovati ◽  
Pouyan Nasiri ◽  
Roozbeh Dargazany

Abstract Material parameters related to deterministic models can have different values due to variation of experiments outcome. From a mathematical point of view, probabilistic modeling can improve this problem. It means that material parameters of constitutive models can be characterized as random variables with a probability distribution. To this end, we propose a constitutive models of rubber-like materials based on uncertainty quantification (UQ) approach. UQ reduces uncertainties in both computational and real-world applications. Constitutive models in elastomers play a crucial role in both science and industry due to their unique hyper-elastic behavior under different loading conditions (uni-axial extension, biaxial, or pure shear). Here our goal is to model the uncertainty in constitutive models of elastomers, and accordingly, identify sensitive parameters that we highly contribute to model uncertainty and error. Modern UQ models can be implemented to use the physics of the problem compared to black-box machine learning approaches that uses data only. In this research, we propagate uncertainty through the model, characterize sensitivity of material behavior to show the importance of each parameter for uncertainty reduction. To this end, we utilized Bayesian rules to develop a model considering uncertainty in the mechanical response of elastomers. As an important assumption, we believe that our measurements are around the model prediction, but it is contaminated by Gaussian noise. We can make the noise by maximizing the posterior. The uni-axial extension experimental data set is used to calibrate the model and propagate uncertainty in this research.


2006 ◽  
Vol 291 (4) ◽  
pp. H1602-H1613 ◽  
Author(s):  
Jean-Hugues Parmentier ◽  
Chunxiang Zhang ◽  
Anne Estes ◽  
Susan Schaefer ◽  
Kafait U. Malik

The contribution of atypical protein kinase C (PKC)-ζ to ANG II-accelerated restenosis after endoluminal vascular injury was investigated by using the rat carotid balloon injury model. Exposure of injured arteries to ANG II resulted in an extensive neointimal thickening (1.9 times) compared with vehicle at day 14. Treatment with PKC-ζ antisense, but not scrambled, oligonucleotides reduced neointimal formation observed in the presence or absence of ANG II. Examination of early events (2 days) after injury showed an increase in cellularity in the perivascular area of the artery wall that was transferred to the adventitia and media after exposure to ANG II, events blocked by PKC-ζ antisense, but not scrambled, oligonucleotides. A positive correlation between medial cellularity at day 2 and extent of neointimal growth at day 14 was established. Immunohistochemical analysis showed that upregulation of inflammatory markers after injury, as well as infiltration of ED1+monocytes/macrophages from the perivascular area to the adventitia, was accelerated by ANG II. However, ANG II-stimulated medial increase in cellularity was proliferation independent, and these cells were monocyte chemoattractant protein-1+/vimentin+but ED1−/VCAM−. PKC-ζ is degraded after injury, and inhibition of its neosynthesis in medial vascular smooth muscle cells or in infiltrating cells with PKC-ζ antisense attenuated medial cellularity and expression of inflammation mediators without reversing smooth muscle cell dedifferentiation. Together, these data indicate that PKC-ζ plays a critical role in normal and ANG II-accelerated neointimal growth through a mechanism involving upregulation of inflammatory mediators, leading to cell infiltration in the media of the vascular wall.


2022 ◽  
Vol 119 (3) ◽  
pp. e2117232119
Author(s):  
Giulio Franchini ◽  
Ivan D. Breslavsky ◽  
Francesco Giovanniello ◽  
Ali Kassab ◽  
Gerhard A. Holzapfel ◽  
...  

Experimental data and a suitable material model for human aortas with smooth muscle activation are not available in the literature despite the need for developing advanced grafts; the present study closes this gap. Mechanical characterization of human descending thoracic aortas was performed with and without vascular smooth muscle (VSM) activation. Specimens were taken from 13 heart-beating donors. The aortic segments were cooled in Belzer UW solution during transport and tested within a few hours after explantation. VSM activation was achieved through the use of potassium depolarization and noradrenaline as vasoactive agents. In addition to isometric activation experiments, the quasistatic passive and active stress–strain curves were obtained for circumferential and longitudinal strips of the aortic material. This characterization made it possible to create an original mechanical model of the active aortic material that accurately fits the experimental data. The dynamic mechanical characterization was executed using cyclic strain at different frequencies of physiological interest. An initial prestretch, which corresponded to the physiological conditions, was applied before cyclic loading. Dynamic tests made it possible to identify the differences in the viscoelastic behavior of the passive and active tissue. This work illustrates the importance of VSM activation for the static and dynamic mechanical response of human aortas. Most importantly, this study provides material data and a material model for the development of a future generation of active aortic grafts that mimic natural behavior and help regulate blood pressure.


2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Ike dela Peña ◽  
Jae Hoon Cheong

At least two laboratories have independently reported the synthesis of benzofuroindole compounds having potential therapeutic implications in many disease states including those that involve smooth muscle hyperactivity. Through a series ofin vitroscreenings, they demonstrated the efficacy (and selectivity) of these compounds to potentiate large conductance calcium- (Ca2+-) activated K+(BKCa) channels, by far, the most characterized of all Ca2+-dependent K+channels. Interestingly, promising benzofuroindole derivatives such as compound 7 (10H-benzo[4,5]furo[3,2-b]indole) and compound 22 (4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid) both exhibited high bladder (versus aorta) selectivity, making them attractive alternative treatments for bladder overactivity. In recent reports, compound 22 (LDD175 or TBIC) also showed inhibition of ileum and uterine contractions, indicating multiple target tissues, which is not surprising as BKCachannels are ubiquitously expressed in the animal and human tissues. In this paper, the authors discuss the value of benzofuroindole compounds and the challenges that need to be overcome if they were considered as smooth muscle relaxants.


Sign in / Sign up

Export Citation Format

Share Document