Mechanostransduction in Cardiac and Stem-Cell Derived Cardiac Cells

Jacot, Jeffrey G.; Raskin, Anna J.; Omens, Jeffrey H.; McCulloch, Andrew D.; Tung, Leslie

doi:10.1007/978-90-481-2850-1_5

Cited by 5 publications

(2 citation statements)

References 238 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Direct stretch of cardiomyocytes can directly affect the activity of several ion channels and increase gap junction-mediated cell coupling, as reviewed in (Jacot et al, 2009). In maturing cardiomyocytes, experiments on neonatal rat atrial cells found that 13% biaxial strains results in differences in gene expression of specific potassium channels and currents, ultimately resulting in reduced action potential duration (Saygili et al, 2007; Rana et al, 2008).…”

Section: Cardiomyocyte Maturationmentioning

confidence: 99%

Mechanobiology of cardiomyocyte development

Jacot

Martin

Hunt

2010

Journal of Biomechanics

Self Cite

193

174

View full text Add to dashboard Cite

Cardiac cells are under constant, self-generated mechanical stress which can affect the differentiation of stem cells into cardiac myocytes, the development of differentiated cells and the maturation of cells in neonatal mammals. In this article, the effects of direct stretch, electrically induced beating and substrate elasticity on the behavior and development of cardiomyocytes are reviewed, with particular emphasis on the effects of substrate stiffness on cardiomyocyte maturation. In order to relate these observations to in-vivo mechanical conditions, we isolated the left ventricle of Black Swiss mice from embryonic day 13.5 through postnatal day 14 and measured the elastic modulus of the epicardium using atomic force microscope indentation. We found that the elastic modulus of the epicardium significantly changes at birth, from an embryonic value of 12 ± 4 kPa to a neonatal value of 39 ± 7 kPa. This change is in the range shown to significantly affect the development of neonatal cardiomyocytes.

show abstract

Section: Cardiomyocyte Maturationmentioning

confidence: 99%

Mechanobiology of cardiomyocyte development

Jacot

Martin

Hunt

2010

Journal of Biomechanics

Self Cite

193

174

View full text Add to dashboard Cite

show abstract

“…In multiple experiments, a relation between strain and conduction velocity (CV) is shown, from which an overview is given in the review of Jacot et al ( Jacot et al, 2010 ). Notably, in a series of studies, an increase in CV was observed for higher strain amplitudes in pulsatile stretch experiments with myocyte cultures ( Wang et al, 2000 ; Zhuang et al, 2000 ; Shyu et al, 2001 ; Pimentel et al, 2002 ; Shanker et al, 2005 ).…”

Section: Introductionmentioning

confidence: 99%

Strain-controlled electrophysiological wave propagation alters in silico scar-based substrate for ventricular tachycardia

Willems,

Janssens,

Dekker

et al. 2024

Front. Physiol.

View full text Add to dashboard Cite

Introduction: Assessing a patient’s risk of scar-based ventricular tachycardia (VT) after myocardial infarction is a challenging task. It can take months to years after infarction for VT to occur. Also, if selected for ablation therapy, success rates are low.Methods: Computational ventricular models have been presented previously to support VT risk assessment and to provide ablation guidance. In this study, an extension to such virtual-heart models is proposed to phenomenologically incorporate tissue remodeling driven by mechanical load. Strain amplitudes in the heart muscle are obtained from simulations of mechanics and are used to adjust the electrical conductivity. Results: The mechanics-driven adaptation of electrophysiology resulted in a more heterogeneous distribution of propagation velocities than that of standard models, which adapt electrophysiology in the structural substrate from medical images only. Moreover, conduction slowing was not only present in such a structural substrate, but extended in the adjacent functional border zone with impaired mechanics. This enlarged the volumes with high repolarization time gradients (≥10 ms/mm). However, maximum gradient values were not significantly affected. The enlarged volumes were localized along the structural substrate border, which lengthened the line of conduction block. The prolonged reentry pathways together with conduction slowing in functional regions increased VT cycle time, such that VT was easier to induce, and the number of recommended ablation sites increased from 3 to 5 locations.Discussion: Sensitivity testing showed an accurate model of strain-dependency to be critical for low ranges of conductivity. The model extension with mechanics-driven tissue remodeling is a potential approach to capture the evolution of the functional substrate and may offer insight into the progression of VT risk over time.

show abstract