scholarly journals Evaluation of fundamental hypotheses underlying constrained mixture models of arterial growth and remodelling

2009 ◽  
Vol 367 (1902) ◽  
pp. 3585-3606 ◽  
Author(s):  
A. Valentín ◽  
J. D. Humphrey
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Mixture Models ◽  
Soft Tissues ◽  
Mass Density ◽  
Constitutive Relations ◽  
Muscle Cells ◽  
Combined Effects ◽  
Mechanical Stimuli ◽  
Constrained Mixture

Evolving constituent composition and organization are important determinants of the biomechanical behaviour of soft tissues. In arteries, vascular smooth muscle cells and fibroblasts continually produce and degrade matrix constituents in preferred modes and at altered rates in response to changing mechanical stimuli. Smooth muscle cells similarly exhibit vasoactive changes that contribute to the control of overall structure, function and mechanical behaviour. Constrained mixture models provide a useful framework in which to quantify arterial growth and remodelling for they can account for cell-mediated changes in individual structurally significant constituents. Our simulations show that the combined effects of changing mass density turnover and vasoactivity, as well as the prestretch at which constituents are incorporated within extant matrix, are essential to capture salient features of bounded arterial growth and remodelling. These findings emphasize the importance of formulating biologically motivated constitutive relations in any theory of growth and remodelling and distinct advantages of the constrained mixture approach, in particular.

Mechanotransduction in gastrointestinal smooth muscle cells: Role of mechanosensitive ion channels

2021 ◽  
Author(s):  
Vikram Joshi ◽  
Peter R Strege ◽  
Gianrico Farrugia ◽  
Arthur Beyder
Keyword(s):  
Smooth Muscle ◽  
Ion Channels ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Tissue Level ◽  
Cytoskeletal Proteins ◽  
Cell Junction ◽  
Mechanical Stimuli ◽  
Junction Molecules

Mechanosensation, the ability to properly sense mechanical stimuli and transduce them into physiologic responses, is an essential determinant of gastrointestinal (GI) function. Abnormalities in this process result in highly prevalent GI functional and motility disorders. In the GI tract, several cell types sense mechanical forces and transduce them into electrical signals, which elicit specific cellular responses. Some mechanosensitive cells like sensory neurons act as specialized mechanosensitive cells that detect forces and transduce signals into tissue-level physiologic reactions. Non-specialized mechanosensitive cells like smooth muscle cells (SMCs) adjust their function in response to forces. Mechanosensitive cells utilize various mechanoreceptors and mechanotransducers. Mechanoreceptors detect and convert force into electrical and biochemical signals, and mechanotransducers amplify and direct mechanoreceptor responses. Mechanoreceptors and mechanotransducers include ion channels, specialized cytoskeletal proteins, cell junction molecules, and G-protein coupled receptors. SMCs are particularly important due to their role as final effectors for motor function. Myogenic reflex-the ability of smooth muscle to contract in response to stretch rapidly-is a critical smooth muscle function. Such rapid mechanotransduction responses rely on mechano-gated and -sensitive ion channels, which alter their ion pores' opening in response to force, allowing fast electrical and Ca2+ responses. Though GI SMCs express a variety of such ion channels, their identities remain unknown. Recent advancements in electrophysiological, genetic, in vivo imaging, and multi-omic technologies broaden our understanding of how SMC mechano-gated and -sensitive ion channels regulate GI functions. This review discusses GI SMC mechanosensitivity's current developments with a particular emphasis on mechano-gated and -sensitive ion channels.

scholarly journals Mechanical stretch is a highly selective regulator of gene expression in human bladder smooth muscle cells

2004 ◽  
Vol 20 (1) ◽  
pp. 36-44 ◽  
Author(s):  
Rosalyn M. Adam ◽  
Samuel H. Eaton ◽  
Carlos Estrada ◽  
Ashish Nimgaonkar ◽  
Shu-Ching Shih ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Ex Vivo ◽  
Muscle Cells ◽  
Mechanical Stimuli ◽  
Bladder Smooth Muscle ◽  
Human Bladder ◽  
Cox 2

Application of mechanical stimuli has been shown to alter gene expression in bladder smooth muscle cells (SMC). To date, only a limited number of “stretch-responsive” genes in this cell type have been reported. We employed oligonucleotide arrays to identify stretch-sensitive genes in primary culture human bladder SMC subjected to repetitive mechanical stimulation for 4 h. Differential gene expression between stretched and nonstretched cells was assessed using Significance Analysis of Microarrays (SAM). Expression of 20 out of 11,731 expressed genes (∼0.17%) was altered >2-fold following stretch, with 19 genes induced and one gene (FGF-9) repressed. Using real-time RT-PCR, we tested independently the responsiveness of 15 genes to stretch and to platelet-derived growth factor-BB (PDGF-BB), another hypertrophic stimulus for bladder SMC. In response to both stimuli, expression of 13 genes increased, 1 gene (FGF-9) decreased, and 1 gene was unchanged. Six transcripts (HB-EGF, BMP-2, COX-2, LIF, PAR-2, and FGF-9) were evaluated using an ex vivo rat model of bladder distension. HB-EGF, BMP-2, COX-2, LIF, and PAR-2 increased with bladder stretch ex vivo, whereas FGF-9 decreased, consistent with expression changes observed in vitro. In silico analysis of microarray data using the FIRED algorithm identified c-jun, AP-1, ATF-2, and neurofibromin-1 (NF-1) as potential transcriptional mediators of stretch signals. Furthermore, the promoters of 9 of 13 stretch-responsive genes contained AP-1 binding sites. These observations identify stretch as a highly selective regulator of gene expression in bladder SMC. Moreover, they suggest that mechanical and growth factor signals converge on common transcriptional regulators that include members of the AP-1 family.

Microtubule assembly is regulated by externally applied strain in cultured smooth muscle cells

1998 ◽  
Vol 111 (22) ◽  
pp. 3379-3387 ◽  
Author(s):  
A.J. Putnam ◽  
J.J. Cunningham ◽  
R.G. Dennis ◽  
J.J. Linderman ◽  
D.J. Mooney
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cultured Cells ◽  
Muscle Cells ◽  
Cellular Protein ◽  
Bovine Brain ◽  
Applied Strain ◽  
Microtubule Assembly ◽  
Mechanical Forces ◽  
Mechanical Stimuli

Mechanical forces clearly regulate the development and phenotype of a variety of tissues and cultured cells. However, it is not clear how mechanical information is transduced intracellularly to alter cellular function. Thermodynamic modeling predicts that mechanical forces influence microtubule assembly, and hence suggest microtubules as one potential cytoskeletal target for mechanical signals. In this study, the assembly of microtubules was analyzed in rat aortic smooth muscle cells cultured on silicon rubber substrates exposed to step increases in applied strain. Cytoskeletal and total cellular protein fractions were extracted from the cells following application of the external strain, and tubulin levels were quantified biochemically via a competitive ELISA and western blotting using bovine brain tubulin as a standard. In the first set of experiments, smooth muscle cells were subjected to a step-increase in strain and the distribution of tubulin between monomeric, polymeric, and total cellular pools was followed with time. Microtubule mass increased rapidly following application of the strain, with a statistically significant increase (P<0.05) in microtubule mass from 373+/−32 pg/cell (t=0) to 514+/−30 pg/cell (t=15 minutes). In parallel, the amount of soluble tubulin decreased approximately fivefold. The microtubule mass decreased after 1 hour to a value of 437+/−24 pg/cell. In the second set of experiments, smooth muscle cells were subjected to increasing doses of externally applied strain using a custom-built strain device. Monomeric, polymeric, and total tubulin fractions were extracted after 15 minutes of applied strain and quantified as for the earlier experiments. Microtubule mass increased with increasing strain while total cellular tubulin levels remained essentially constant at all strain levels. These findings are consistent with a thermodynamic model which predicts that microtubule assembly is promoted as a cell is stretched and compressional loads on the microtubules are presumably relieved. Furthermore, these data suggest microtubules are a potential target for translating changes in externally applied mechanical stimuli to alterations in cellular phenotype.

scholarly journals Cyclic mechanical stretch up-regulates hepatoma-derived growth factor expression in cultured rat aortic smooth muscle cells

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Ying-Hsien Kao ◽  
Po-Han Chen ◽  
Cheuk-Kwan Sun ◽  
Yo-Chen Chang ◽  
Yu-Chun Lin ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Constitutive Expression ◽  
Muscle Cells ◽  
Mechanical Stretch ◽  
Morphological Observation ◽  
Mechanical Stimuli ◽  
Vascular Walls ◽  
Tnf Α

Hepatoma-derived growth factor (HDGF) is a potent mitogen for vascular smooth muscle cells (SMCs) during embryogenesis and injury repair of vessel walls. Whether mechanical stimuli modulate HDGF expression remains unknown. The present study aimed at investigating whether cyclic mechanical stretch plays a regulatory role in HDGF expression and regenerative cytokine production in aortic SMCs. A SMC cell line was grown on a silicone-based elastomer chamber with extracellular matrix coatings (either type I collagen or fibronectin) and received cyclic and uniaxial mechanical stretches with 10% deformation at frequency 1 Hz. Morphological observation showed that fibronectin coating provided better cell adhesion and spreading and that consecutive 6 h of cyclic mechanical stretch remarkably induced reorientation and realignment of SMCs. Western blotting detection demonstrated that continuous mechanical stimuli elicited up-regulation of HDGF and proliferative cell nuclear antigen, a cell proliferative marker. Signal kinetic profiling study indicated that cyclic mechanical stretch induced signaling activity in RhoA/ROCK and PI3K/Akt cascades. Kinase inhibition study further showed that blockade of PI3K activity suppressed the stretch-induced tumor necrosis factor-α (TNF-α), whereas RhoA/ROCK inhibition significantly blunted the interleukin-6 (IL-6) production and HDGF overexpression. Moreover, siRNA-mediated HDGF gene silencing significantly suppressed constitutive expression of IL-6, but not TNF-α, in SMCs. These findings support the role of HDGF in maintaining vascular expression of IL-6, which has been regarded a crucial regenerative factor for acute vascular injury. In conclusion, cyclic mechanical stretch may maintain constitutive expression of HDGF in vascular walls and be regarded an important biophysical regulator in vascular regeneration.

Cellular Response to Stretch by Modulation of Cytoskeletal Tension in Two Distinct Phases

2011 ◽  
Author(s):  
Jennifer Mann ◽  
Raymond Lam ◽  
Jianping Fu
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cellular Response ◽  
Cell Structure ◽  
Muscle Cells ◽  
Underlying Mechanism ◽  
Dynamic Responses ◽  
Mechanistic Study ◽  
Mechanical Stimuli ◽  
External Forces

External forces are increasingly recognized as major regulators of cell structure and function, yet the underlying mechanism by which cells sense force and transduce it into intracellular biochemical signals and behavioral responses (‘mechanotransduction’) is largely undetermined. To aid in the mechanistic study of mechanotransduction, we devised a novel cell stretching device that allows for quantitative control and real-time measurement of mechanical stimuli and cellular biomechanical responses. Using this device, we studied the subcellular dynamic responses of contractile force and adhesion remodeling of vascular smooth muscle cells (VSMCs) to stretch. Our data showed that VSMCs could acutely enhance their contraction to resist rapid cell deformation, but they could also allow slow adaptive inelastic cytoskeletal reorganization in response to sustained cell stretch. Our study may help elucidate the mechanotransduction system in smooth muscle cells, and thus contribute to our understanding of pressure-induced vascular disease processes.

Hyposmotic challenge inhibits inward rectifying K+ channels in cerebral arterial smooth muscle cells

2007 ◽  
Vol 292 (2) ◽  
pp. H1085-H1094 ◽  
Author(s):  
Bin-Nan Wu ◽  
Kevin D. Luykenaar ◽  
Joseph E. Brayden ◽  
Wayne R. Giles ◽  
Randolph L. Corteling ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cerebral Arteries ◽  
Muscle Cells ◽  
Delayed Rectifier ◽  
Mechanical Stimuli ◽  
Arterial Smooth Muscle ◽  
Voltage Dependent ◽  
Arterial Smooth Muscle Cells ◽  
Patch Clamp Electrophysiology

This study sought to define whether inward rectifying K+ (KIR) channels were modulated by vasoactive stimuli known to depolarize and constrict intact cerebral arteries. Using pressure myography and patch-clamp electrophysiology, initial experiments revealed a Ba2+-sensitive KIR current in cerebral arterial smooth muscle cells that was active over a physiological range of membrane potentials and whose inhibition led to arterial depolarization and constriction. Real-time PCR, Western blot, and immunohistochemical analyses established the expression of both KIR2.1 and KIR2.2 in cerebral arterial smooth muscle cells. Vasoconstrictor agonists known to depolarize and constrict rat cerebral arteries, including uridine triphosphate, U46619, and 5-HT, had no discernable effect on whole cell KIR activity. Control experiments confirmed that vasoconstrictor agonists could inhibit the voltage-dependent delayed rectifier K+ (KDR) current. In contrast to these observations, a hyposmotic challenge that activates mechanosensitive ion channels elicited a rapid and sustained inhibition of the KIR but not the KDR current. The hyposmotic-induced inhibition of KIR was 1) mimicked by phorbol-12-myristate-13-acetate, a PKC agonist; and 2) inhibited by calphostin C, a PKC inhibitor. These findings suggest that, by modulating PKC, mechanical stimuli can regulate KIR activity and consequently the electrical and mechanical state of intact cerebral arteries. We propose that the mechanoregulation of KIR channels plays a role in the development of myogenic tone.

Construction of Functional Soft Tissues From Premodulated Smooth Muscle Cells Using a Bioreactor System

2006 ◽  
Vol 30 (9) ◽  
pp. 704-707 ◽  
Author(s):  
Jae Min Cha ◽  
Si-Nae Park ◽  
Guen-Oh Park ◽  
Jeong Koo Kim ◽  
Hwal Suh
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Soft Tissues ◽  
Muscle Cells ◽  
Bioreactor System

Immunogold localization of HMB-45 antigen in pulmonary lymphangiomyomatosis

1995 ◽  
Vol 53 ◽  
pp. 998-999
Author(s):  
J.M. Minda ◽  
E. Dessy ◽  
G. G. Pietra
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Room Temperature ◽  
Osmium Tetroxide ◽  
Muscle Cells ◽  
Ultrastructural Localization ◽  
Reproductive Age ◽  
Thin Sections ◽  
Smooth Muscle Proliferation ◽  
Hmb 45

Pulmonary lymphangiomyomatosis (PLAM) is a rare disease occurring exclusively in women of reproductive age. It involves the lungs, lymph nodes and lymphatic ducts. In the lungs, it is characterized by the proliferation of smooth muscle cells around lymphatics in the bronchovascular bundles, lobular septa and pleura The nature of smooth muscle proliferation in PLAM is still unclear. Recently, reactivity of the smooth muscle cells for HMB-45, a melanoma-related antigen has been reported by immunohistochemistry. The purpose of this study was the ultrastructural localization of HMB-45 immunoreactivity in these cells using gold-labeled antibodies.Lung tissue from three cases of PLAM, referred to our Institution for lung transplantation, was embedded in either Poly/Bed 812 post-fixed in 1% osmium tetroxide, or in LR White, without osmication. For the immunogold technique, thin sections were placed on Nickel grids and incubated with affinity purified, monoclonal anti-melanoma antibody HMB-45 (1:1) (Enzo Diag. Co) overnight at 4°C. After extensive washing with PBS, grids were treated with Goat-anti-mouse-IgG-Gold (5nm) (1:10) (Amersham Life Sci) for 1 hour, at room temperature.

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