Length adaptation of smooth muscle contractile filaments in response to sustained activation

Stålhand, Jonas; Holzapfel, Gerhard

doi:10.1016/j.jtbi.2016.02.028

Cited by 15 publications

(5 citation statements)

References 37 publications

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“… 105 , 106 Prolonged vasoconstriction and associated actin polymerization participate in the initial phases of vascular remodelling in hypertension, processes that involve ROCK and ROS. 107 Vascular smooth muscle cell length adaptation, with reorganization of the actin cytoskeleton also contributes to small artery eutrophic remodelling, typically observed in essential hypertension. 108 …”

Section: The Actin Cytoskeleton and Contractionmentioning

confidence: 99%

Vascular smooth muscle contraction in hypertension

Touyz

Alves-Lopes

Ríos

et al. 2018

Cardiovascular Research

483

316

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Hypertension is a major risk factor for many common chronic diseases, such as heart failure, myocardial infarction, stroke, vascular dementia, and chronic kidney disease. Pathophysiological mechanisms contributing to the development of hypertension include increased vascular resistance, determined in large part by reduced vascular diameter due to increased vascular contraction and arterial remodelling. These processes are regulated by complex-interacting systems such as the renin-angiotensin-aldosterone system, sympathetic nervous system, immune activation, and oxidative stress, which influence vascular smooth muscle function. Vascular smooth muscle cells are highly plastic and in pathological conditions undergo phenotypic changes from a contractile to a proliferative state. Vascular smooth muscle contraction is triggered by an increase in intracellular free calcium concentration ([Ca2+]i), promoting actin–myosin cross-bridge formation. Growing evidence indicates that contraction is also regulated by calcium-independent mechanisms involving RhoA-Rho kinase, protein Kinase C and mitogen-activated protein kinase signalling, reactive oxygen species, and reorganization of the actin cytoskeleton. Activation of immune/inflammatory pathways and non-coding RNAs are also emerging as important regulators of vascular function. Vascular smooth muscle cell [Ca2+]i not only determines the contractile state but also influences activity of many calcium-dependent transcription factors and proteins thereby impacting the cellular phenotype and function. Perturbations in vascular smooth muscle cell signalling and altered function influence vascular reactivity and tone, important determinants of vascular resistance and blood pressure. Here, we discuss mechanisms regulating vascular reactivity and contraction in physiological and pathophysiological conditions and highlight some new advances in the field, focusing specifically on hypertension.

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Section: The Actin Cytoskeleton and Contractionmentioning

confidence: 99%

Vascular smooth muscle contraction in hypertension

Touyz

Alves-Lopes

Ríos

et al. 2018

Cardiovascular Research

483

316

View full text Add to dashboard Cite

show abstract

“…( 2018 ), Murtada et al. ( 2017 ) and Stålhand and Holzapfel ( 2016 ). However, while this effect can have considerable impact on the degree of contraction, the majority of reports in biology and medicine (see, e.g., Wray 2010 ; Cole and Welsh 2011 ; Tykocki et al.…”

Section: Introductionmentioning

confidence: 98%

Chemo-mechanical modeling of smooth muscle cell activation for the simulation of arterial walls under changing blood pressure

Uhlmann

Balzani

2023

Biomech Model Mechanobiol

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In this paper, a novel chemo-mechanical model is proposed for the description of the stretch-dependent chemical processes known as Bayliss effect and their impact on the active contraction in vascular smooth muscle. These processes are responsible for the adaptive reaction of arterial walls to changing blood pressure by which the blood vessels actively support the heart in providing sufficient blood supply for varying demands in the supplied tissues. The model is designed to describe two different stretch-dependent mechanisms observed in smooth muscle cells (SMCs): a calcium-dependent and a calcium-independent contraction. For the first one, stretch of the SMCs leads to an inlet of calcium ions which activates the myosin light chain kinase (MLCK). The increased activity of MLCK triggers the contractile units of the cells resulting in the contraction on a comparatively short time scale. For the calcium-independent contraction mechanism, stretch-dependent receptors of the cell membrane stimulate an intracellular reaction leading to an inhibition of the antagonist of MLCK, the myosin light chain phosphatase resulting in a contraction on a comparatively long time scale. An algorithmic framework for the implementation of the model in finite element programs is derived. Based thereon, it is shown that the proposed approach agrees well with experimental data. Furthermore, the individual aspects of the model are analyzed in numerical simulations of idealized arteries subject to internal pressure waves with changing intensities. The simulations show that the proposed model is able to describe the experimentally observed contraction of the artery as a reaction to increased internal pressure, which can be considered a crucial aspect of the regulatory mechanism of muscular arteries.

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“…68,69 Beyond their immediate response to stretch, smooth muscle cells can also adapt to sustained stretch by remodeling their cytoskeleton. 70,71 The adaptation of vascular smooth muscle cells has been characterized in vitro by culturing cells on stretchable membranes and measuring force generation at different timepoints after sustained stretch. After 1 h of stretch, vascular smooth muscle cells have higher basal tone, which approaches un-stretched levels of basal tone after 24 h. 72 Similar results have been observed in airway smooth muscle cells.…”

Section: Measuring Contractility In Response To Biomechanical Stimuli In Vitromentioning

confidence: 99%

Tools, techniques, and future opportunities for characterizing the mechanobiology of uterine myometrium

Maxey

McCain

2021

Exp Biol Med (Maywood)

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The myometrium is the smooth muscle layer of the uterus that generates the contractions that drive processes such as menstruation and childbirth. Aberrant contractions of the myometrium can result in preterm birth, insufficient progression of labor, or other difficulties that can lead to maternal or fetal complications or even death. To investigate the underlying mechanisms of these conditions, the most common model systems have conventionally been animal models and human tissue strips, which have limitations mostly related to relevance and scalability, respectively. Myometrial smooth muscle cells have also been isolated from patient biopsies and cultured in vitro as a more controlled experimental system. However, in vitro approaches have focused primarily on measuring the effects of biochemical stimuli and neglected biomechanical stimuli, despite the extensive evidence indicating that remodeling of tissue rigidity or excessive strain is associated with uterine disorders. In this review, we first describe the existing approaches for modeling human myometrium with animal models and human tissue strips and compare their advantages and disadvantages. Next, we introduce existing in vitro techniques and assays for assessing contractility and summarize their applications in elucidating the role of biochemical or biomechanical stimuli on human myometrium. Finally, we conclude by proposing the translation of “organ on chip” approaches to myometrial smooth muscle cells as new paradigms for establishing their fundamental mechanobiology and to serve as next-generation platforms for drug development.

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Length adaptation of smooth muscle contractile filaments in response to sustained activation

Cited by 15 publications

References 37 publications

Vascular smooth muscle contraction in hypertension

Vascular smooth muscle contraction in hypertension

Chemo-mechanical modeling of smooth muscle cell activation for the simulation of arterial walls under changing blood pressure

Tools, techniques, and future opportunities for characterizing the mechanobiology of uterine myometrium

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