Mechanobiology in cardiac physiology and diseases

Takahashi, Katsuroku; Kakimoto, Yoshihide; Toda, Kensaku; Naruse, Keiji

doi:10.1111/jcmm.12027

Cited by 60 publications

(61 citation statements)

References 93 publications

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“…The application of specific physical stimuli in a tailored bioreactor emerged as an appropriate strategy to obtain a bioengineered cardiac tissue, where mechanotransduction is known to play a significant role [37]. The initial evidence of effectiveness of mechanostimulation protocols in cardiac tissue engineering dates back to the second half of the nineties, when Vandenburgh et al [38] showed that unidirectional mechanical stretch initiated in vitro a number of morphological alterations in a confluent cardiomyocyte population which were similar to those occurring during in vivo heart growth.…”

Section: Bioreactors For Cardiac Tissue Engineeringmentioning

confidence: 99%

Mechanostimulation Protocols for Cardiac Tissue Engineering

Govoni

Muscari

Guarnieri

et al. 2013

BioMed Research International

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Owing to the inability of self-replacement by a damaged myocardium, alternative strategies to heart transplantation have been explored within the last decades and cardiac tissue engineering/regenerative medicine is among the present challenges in biomedical research. Hopefully, several studies witness the constant extension of the toolbox available to engineer a fully functional, contractile, and robust cardiac tissue using different combinations of cells, template bioscaffolds, and biophysical stimuli obtained by the use of specific bioreactors. Mechanical forces influence the growth and shape of every tissue in our body generating changes in intracellular biochemistry and gene expression. That is why bioreactors play a central role in the task of regenerating a complex tissue such as the myocardium. In the last fifteen years a large number of dynamic culture devices have been developed and many results have been collected. The aim of this brief review is to resume in a single streamlined paper the state of the art in this field.

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Section: Bioreactors For Cardiac Tissue Engineeringmentioning

confidence: 99%

Mechanostimulation Protocols for Cardiac Tissue Engineering

Govoni

Muscari

Guarnieri

et al. 2013

BioMed Research International

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“…Beyond this, the importance of mechanoelectric feedback adds another layer of complexity to cardiac mechanotransduction. For instance, ion channels such as Cav1.2 and the TRP family of ion channels have specific locations in the heart and enable organ level responses to pressure and volume fluctuations by helping regulate action potentials (Takahashi et al, 2013). Connexins, transmembrane proteins important for gap junction formation, may act as effectors to coordinate excitation-contraction coupling (Meens et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Cellular mechanosensing: Getting to the nucleus of it all

Fedorchak

Kaminski

Lammerding

2014

Progress in Biophysics and Molecular Biology

165

152

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Cells respond to mechanical forces by activating specific genes and signaling pathways that allow the cells to adapt to their physical environment. Examples include muscle growth in response to exercise, bone remodeling based on their mechanical load, or endothelial cells aligning under fluid shear stress. While the involved downstream signaling pathways and mechanoresponsive genes are generally well characterized, many of the molecular mechanisms of the initiating ‘mechanosensing’ remain still elusive. In this review, we discuss recent findings and accumulating evidence suggesting that the cell nucleus plays a crucial role in cellular mechanotransduction, including processing incoming mechanoresponsive signals and even directly responding to mechanical forces. Consequently, mutations in the involved proteins or changes in nuclear envelope composition can directly impact mechanotransduction signaling and contribute to the development and progression of a variety of human diseases, including muscular dystrophy, cancer, and the focus of this review, dilated cardiomyopathy. Improved insights into the molecular mechanisms underlying nuclear mechanotransduction, brought in part by the emergence of new technologies to study intracellular mechanics at high spatial and temporal resolution, will not only result in a better understanding of cellular mechanosensing in normal cells but may also lead to the development of novel therapies in the many diseases linked to defects in nuclear envelope proteins.

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“…165 It has been implicated in stretch-activated responses of vascular smooth muscle. 179 Overexpression of TRPM4 may be involved in an inheritable form of progressive familial heart block type I, 67 though perhaps via mechanisms not directly related to TRPM4 mechano-sensitivity. Its physiological role in the heart is currently unknown.…”

Section: Cardiac Sac: Molecular Candidatesmentioning

confidence: 99%

“…66 Interestingly, stretch-preconditioning, known to reduce ischaemia-reperfusion injury, is abolished by blocking K ATP channels. 67 Of note, cardiac K ATP channels are also present and active in fibroblasts, suggesting that one must consider cardiac pre-/post-conditioning effects on cells other than just cardiomyocytes. 68–70 As with other K + channels, K ATP opening favours re-/hyperpolarization.…”

Section: Introduction To Cardiac Mechano-sensitivitymentioning

confidence: 99%

Cardiac Mechano-Gated Ion Channels and Arrhythmias

Peyronnet

Nerbonne

Kohl

2016

Circulation Research

179

167

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Mechanical forces will have been omnipresent since the origin of life, and living organisms have evolved mechanisms to sense, interpret and respond to mechanical stimuli. The cardiovascular system in general, and the heart in particular, are exposed to constantly changing mechanical signals, including stretch, compression, bending, and shear. The heart adjusts its performance to the mechanical environment, modifying electrical, mechanical, metabolic, and structural properties over a range of time scales. Many of the underlying regulatory processes are encoded intra-cardially, and are thus maintained even in heart transplant recipients. Although mechano-sensitivity of heart rhythm has been described in the medical literature for over a century, its molecular mechanisms are incompletely understood. Thanks to modern biophysical and molecular technologies, the roles of mechanical forces in cardiac biology are being explored in more detail, and detailed mechanisms of mechano-transduction have started to emerge. Mechano-gated ion channels are cardiac mechano-receptors. They give rise to mechano-electric feedback, thought to contribute to normal function, disease development, and, potentially, therapeutic interventions. In this review, we focus on acute mechanical effects on cardiac electrophysiology, explore molecular candidates underlying observed responses, and discuss their pharmaceutical regulation. From this, we identify open research questions and highlight emerging technologies that may help in addressing them. Cardiac electrophysiology is acutely affected by the heart’s mechanical environment. Mechano-electric feedback affects excitability, conduction, and electrical load, and remains an underestimated player in arrhythmogenesis. The utility of therapeutic interventions targeting acute mechano-electrical transduction is an open field worthy of further study.

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Mechanobiology in cardiac physiology and diseases

Cited by 60 publications

References 93 publications

Mechanostimulation Protocols for Cardiac Tissue Engineering

Mechanostimulation Protocols for Cardiac Tissue Engineering

Cellular mechanosensing: Getting to the nucleus of it all

Cardiac Mechano-Gated Ion Channels and Arrhythmias

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