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Cellular Signalling May 2018Vascular smooth muscle cells (SMCs) phenotypes span a reversible continuum from quiescent/contractile (differentiated) to proliferative/synthetic (dedifferentiated)... (Review)
Review
Vascular smooth muscle cells (SMCs) phenotypes span a reversible continuum from quiescent/contractile (differentiated) to proliferative/synthetic (dedifferentiated) enabling them to perform a diversity of functions that are context-dependent and important for vascular tone-diameter homeostasis, vasculogenesis, angiogenesis or vessel reparation after injury. Dysregulated phenotype modulation and failure to maintain/regain the mature differentiated and contractile phenotypic state is pivotal in the development of vascular diseases such as atherosclerosis and restenosis after angioplasty and coronary bypass grafting. Many functions of SMCs such as adhesion, migration, proliferation, contraction, differentiation and apoptosis are regulated by a broad spectrum of cell-cell and cell-matrix adhesion molecules. Cadherins represent a superfamily of cell surface homophilic adhesion molecules with fundamental roles in morphogenetic and differentiation processes during development and in the maintenance of tissue integrity and homeostasis in adults. The cadherins have major inputs on signalling pathways and cytoskeletal assemblies that participate in regulating processes such as cell polarity, migration, proliferation, survival, phenotype and differentiation. Abnormalities in these processes have long been recognized to underlie pathological SMC-driven reparation, but knowledge on the involvement of cadherins is remarkably limited. This article presents a comprehensive review of cadherin family members currently identified on vascular SMCs in relation to their functions, molecular mechanisms of action and relevance for vascular pathology.
Topics: Animals; Apoptosis; Atherosclerosis; Cadherins; Cell Adhesion; Cell Differentiation; Cell Movement; Cytoskeleton; Homeostasis; Humans; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Signal Transduction
PubMed: 29413845
DOI: 10.1016/j.cellsig.2018.01.023 -
Biomaterials Advances Jun 2022Understanding how nanostructured coatings interact with cells is related to how they manipulate cell behaviors and is therefore critical for designing better...
Understanding how nanostructured coatings interact with cells is related to how they manipulate cell behaviors and is therefore critical for designing better biomaterials. The apatite nanosheets were deposited on metallic substrates via biomimetic precipitation. Cell viability of apatite nanosheets towards to smooth muscle cells (SMCs) were investigated, and the underlying mechanism was proposed. Apatite nanosheets presented inhibitory activity on SMC growth, and caused rupture of cell membranes. On the basis of measuring changes in intracellular calcium ([Ca]), observing cell contraction and apatite nanosheets - SMC interaction, it was found that calcium ions released from apatite led to rises in [Ca], which induced vigorous SMC contraction on apatite nanosheets. Consequently, the cell membrane of individual SMCs was cut/penetrated by the sharp edges of apatite nanosheets, resulting in cell inactivation. This damage of cell membranes suggests a novel mechanism to manipulate cell viability, and may offer insights for the better design of calcium-based nanostructured coatings or other biomedical applications.
Topics: Apatites; Biomimetics; Cell Membrane; Cell Proliferation; Myocytes, Smooth Muscle
PubMed: 35929280
DOI: 10.1016/j.bioadv.2022.212852 -
Cellular Signalling Jan 2019Excessive vascular smooth muscle cell (SMC) proliferation, migration and extracellular matrix (ECM) synthesis are key events in the development of intimal hyperplasia, a... (Review)
Review
Excessive vascular smooth muscle cell (SMC) proliferation, migration and extracellular matrix (ECM) synthesis are key events in the development of intimal hyperplasia, a pathophysiological response to acute or chronic sources of vascular damage that can lead to occlusive narrowing of the vessel lumen. Atherosclerosis, the primary cause of coronary artery disease, is characterised by chronic vascular inflammation and dyslipidemia, while revascularisation surgeries such as coronary stenting and bypass grafting represent acute forms of vascular injury. Gene knockouts of transforming growth factor-beta (TGFβ), its receptors and downstream signalling proteins have demonstrated the importance of this pleiotropic cytokine during vasculogenesis and in the maintenance of vascular homeostasis. Dysregulated TGFβ signalling is a hallmark of many vascular diseases, and has been associated with the induction of pathological vascular cell phenotypes, fibrosis and ECM remodelling. Here we present an overview of TGFβ signalling in SMCs, highlighting the ways in which this multifaceted cytokine regulates SMC behaviour and phenotype in cardiovascular diseases driven by intimal hyperplasia.
Topics: Animals; Cell Movement; Cell Proliferation; Coronary Artery Disease; Humans; Myocytes, Smooth Muscle; Signal Transduction; Transforming Growth Factor beta
PubMed: 30227237
DOI: 10.1016/j.cellsig.2018.09.004 -
International Journal of Molecular... Sep 2021Arteriogenesis is one of the primary physiological means by which the circulatory collateral system restores blood flow after significant arterial occlusion in... (Review)
Review
Arteriogenesis is one of the primary physiological means by which the circulatory collateral system restores blood flow after significant arterial occlusion in peripheral arterial disease patients. Vascular smooth muscle cells (VSMCs) are the predominant cell type in collateral arteries and respond to altered blood flow and inflammatory conditions after an arterial occlusion by switching their phenotype between quiescent contractile and proliferative synthetic states. Maintaining the contractile state of VSMC is required for collateral vascular function to regulate blood vessel tone and blood flow during arteriogenesis, whereas synthetic SMCs are crucial in the growth and remodeling of the collateral media layer to establish more stable conduit arteries. Timely VSMC phenotype switching requires a set of coordinated actions of molecular and cellular mediators to result in an expansive remodeling of collaterals that restores the blood flow effectively into downstream ischemic tissues. This review overviews the role of VSMC phenotypic switching in the physiological arteriogenesis process and how the VSMC phenotype is affected by the primary triggers of arteriogenesis such as blood flow hemodynamic forces and inflammation. Better understanding the role of VSMC phenotype switching during arteriogenesis can identify novel therapeutic strategies to enhance revascularization in peripheral arterial disease.
Topics: Animals; Arterial Occlusive Diseases; Arteries; Cell Proliferation; Collateral Circulation; Gene Expression; Humans; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phenotype; Vascular Remodeling
PubMed: 34638923
DOI: 10.3390/ijms221910585 -
Progress in Biophysics and Molecular... Aug 2014The relatively recent development of microfluidic systems with wide-ranging capabilities for generating realistic 2D or 3D systems with single or multiple cell types has... (Review)
Review
The relatively recent development of microfluidic systems with wide-ranging capabilities for generating realistic 2D or 3D systems with single or multiple cell types has given rise to an extensive collection of platform technologies useful in muscle tissue engineering. These new systems are aimed at (i) gaining fundamental understanding of muscle function, (ii) creating functional muscle constructs in vitro, and (iii) utilizing these constructs a variety of applications. Use of microfluidics to control the various stimuli that promote differentiation of multipotent cells into cardiac or skeletal muscle is first discussed. Next, systems that incorporate muscle cells to produce either 2D sheets or 3D tissues of contractile muscle are described with an emphasis on the more recent 3D platforms. These systems are useful for fundamental studies of muscle biology and can also be incorporated into drug screening assays. Applications are discussed for muscle actuators in the context of microrobotics and in miniaturized biological pumps. Finally, an important area of recent study involves coculture with cell types that either activate muscle or facilitate its function. Limitations of current designs and the potential for improving functionality for a wider range of applications is also discussed, with a look toward using current understanding and capabilities to design systems of greater realism, complexity and functionality.
Topics: Animals; Cells, Cultured; Equipment Design; Equipment Failure Analysis; Humans; Microfluidic Analytical Techniques; Miniaturization; Muscle Cells; Muscle Development; Tissue Engineering; Tissue Scaffolds
PubMed: 25175338
DOI: 10.1016/j.pbiomolbio.2014.08.013 -
Physiological Reviews Oct 2021The design of the energy metabolism system in striated muscle remains a major area of investigation. Here, we review our current understanding and emerging hypotheses... (Review)
Review
The design of the energy metabolism system in striated muscle remains a major area of investigation. Here, we review our current understanding and emerging hypotheses regarding the metabolic support of muscle contraction. Maintenance of ATP free energy, so called energy homeostasis, via mitochondrial oxidative phosphorylation is critical to sustained contractile activity, and this major design criterion is the focus of this review. Cell volume invested in mitochondria reduces the space available for generating contractile force, and this spatial balance between mitochondria acontractile elements to meet the varying sustained power demands across muscle types is another important design criterion. This is accomplished with remarkably similar mass-specific mitochondrial protein composition across muscle types, implying that it is the organization of mitochondria within the muscle cell that is critical to supporting sustained muscle function. Beyond the production of ATP, ubiquitous distribution of ATPases throughout the muscle requires rapid distribution of potential energy across these large cells. Distribution of potential energy has long been thought to occur primarily through facilitated metabolite diffusion, but recent analysis has questioned the importance of this process under normal physiological conditions. Recent structural and functional studies have supported the hypothesis that the mitochondrial reticulum provides a rapid energy distribution system via the conduction of the mitochondrial membrane potential to maintain metabolic homeostasis during contractile activity. We extensively review this aspect of the energy metabolism design contrasting it with metabolite diffusion models and how mitochondrial structure can play a role in the delivery of energy in the striated muscle.
Topics: Animals; Energy Metabolism; Humans; Mitochondria, Muscle; Muscle Cells; Muscle, Striated
PubMed: 33733879
DOI: 10.1152/physrev.00040.2020 -
Molecular Aspects of Medicine Apr 2018Research into the biology of extracellular vesicles (EVs), including exosomes and microvesicles, has expanded significantly with advances in EV isolation techniques, a... (Review)
Review
Research into the biology of extracellular vesicles (EVs), including exosomes and microvesicles, has expanded significantly with advances in EV isolation techniques, a better understanding of the surface markers that characterize exosomes and microvesicles, and greater information derived from -omics approaches on the proteins, lipids, mRNAs, and microRNAs (miRNAs) transported by EVs. We have recently discovered a role for exosome-derived miRNAs in age-related bone loss and osteoarthritis, two conditions that impose a significant public health burden on the aging global population. Previous work has also revealed multiple roles for EVs and their miRNAs in muscle regeneration and congenital myopathies. Thus, EVs appear to be involved in a number of degenerative conditions that impact the musculoskeletal system, indicating that the musculoskeletal system is an excellent model for investigating the role of EVs in tissue maintenance and repair. This review highlights the role of EVs in bone, skeletal muscle, and joint health, including both normal tissue metabolism as well as tissue injury repair and regeneration. A consistent theme that emerges from study of musculoskeletal EVs is that various miRNAs appear to mediate a number of key pathological processes. These findings point to a potential therapeutic opportunity to target EV-derived miRNAs as a strategy for improving musculoskeletal function.
Topics: Animals; Biomarkers; Bone and Bones; Cell Differentiation; Disease Susceptibility; Extracellular Vesicles; Humans; Joint Diseases; Muscle Cells; Musculoskeletal Diseases; Osteoporosis; Regeneration
PubMed: 28965750
DOI: 10.1016/j.mam.2017.09.006 -
Biomolecules Oct 2021(Ashwagandha) is used in Indian traditional medicine, Ayurveda, and is believed to have a variety of health-promoting effects. The molecular mechanisms and pathways...
(Ashwagandha) is used in Indian traditional medicine, Ayurveda, and is believed to have a variety of health-promoting effects. The molecular mechanisms and pathways underlying these effects have not yet been sufficiently explored. In this study, we investigated the effect of Ashwagandha extracts and their major withanolides (withaferin A and withanone) on muscle cell differentiation using C2C12 myoblasts. We found that withaferin A and withanone and Ashwagandha extracts possessing different ratios of these active ingredients have different effects on the differentiation of C2C12. Withanone and withanone-rich extracts caused stronger differentiation of myoblasts to myotubes, deaggregation of heat- and metal-stress-induced aggregated proteins, and activation of hypoxia and autophagy pathways. Of note, the Parkinson's disease model of Drosophila that possess a neuromuscular disorder showed improvement in their flight and climbing activity, suggesting the potential of Ashwagandha withanolides for the management of muscle repair and activity.
Topics: Animals; Cell Differentiation; Cell Line; Humans; Medicine, Ayurvedic; Mice; Muscle Cells; Parkinson Disease; Plant Extracts; Withanolides
PubMed: 34680087
DOI: 10.3390/biom11101454 -
Critical Reviews in Biomedical... 2022This paper presents a review of studies on the effects of local vibration training (LVT) on muscle strength along with the associated changes in neuromuscular and cell... (Review)
Review
This paper presents a review of studies on the effects of local vibration training (LVT) on muscle strength along with the associated changes in neuromuscular and cell dynamic responses. Application of local/direct vibration can significantly change the structural properties of muscle cell and can improve muscle strength. The improvement is largely dependent on vibration parameters such as amplitude and frequency. The results of 20 clinical studies reveal that electromyography (EMG) and maximal voluntary contraction (MVC) vary depending on vibration frequency, and studies using frequencies of 28-30 Hz reported greater increases in muscle activity in terms of EMG (rms) value and MVC data than the studies using higher frequencies. A greater muscle activity can be related to the recruitment of large motor units due to the application of local vibration. A greater increase in EMG (rms) values for biceps and triceps during extension than flexion under LVT suggests that types of muscles and their functions play an important role. Although a number of clinical trials and animal studies have demonstrated positive effects of vibration on muscle, an optimum training protocol has not been established. An attempt is made in this study to investigate the optimal LVT conditions on different muscles through review and analysis of published results in the literature pertaining to the changes in the neuromuscular activity. Directions for future research are discussed with regard to identifying optimal conditions for LVT and better understanding of the mechanisms associated with effects of vibration on muscles.
Topics: Electromyography; Muscle Cells; Muscle Contraction; Muscle Strength; Muscle, Skeletal; Vibration
PubMed: 35997107
DOI: 10.1615/CritRevBiomedEng.2022041625 -
Skeletal Muscle Dec 2021Measuring biological features of skeletal muscle cells is difficult because of their unique morphology and multinucleate nature upon differentiation. Here, we developed...
BACKGROUND
Measuring biological features of skeletal muscle cells is difficult because of their unique morphology and multinucleate nature upon differentiation. Here, we developed a new Fiji macro package called ViaFuse (that stands for viability and fusion) to measure skeletal muscle cell viability and differentiation. To test ViaFuse, we utilized immunofluorescence images of differentiated myotubes where the capping actin protein of muscle z-line subunit beta (CAPZB) was depleted in comparison with control cells.
RESULTS
We compared the values achieved using the ViaFuse macros first with manual quantification performed by researchers and second with those obtained utilizing the MATLAB muscle-centric software MyoCount. We observed a high degree of correlation between all methods of quantification.
CONCLUSIONS
ViaFuse can detect the borders of myotubes and identify nuclear clumps which have been limitations of previous muscle-centric imaging software. The ViaFuse macros require little computer power or space to run and user inputs to the ViaFuse macros are minimal, thereby automating the analysis process in a quick, easy, and accurate fashion. Additionally, the ViaFuse macros work with Fiji, an existing imaging software widely used by skeletal muscle researchers. Furthermore, ViaFuse is compatible with many computer systems, has a very intuitive interface, and does not require prior complex mathematical knowledge. Therefore, we propose ViaFuse as a robust and meticulous method to quantify skeletal muscle cell viability and differentiation.
Topics: Cell Differentiation; Cell Survival; Fiji; Muscle Fibers, Skeletal; Muscle, Skeletal
PubMed: 34915930
DOI: 10.1186/s13395-021-00284-3