Fibroblasts Slow Conduction Velocity in a Reconstituted Tissue Model of Fibrotic Cardiomyopathy

Spencer, Teresa M.; Blumenstein, Ryan F.; Pryse, Kenneth M.; Lee, Sheng-Lin; Glaubke, David A.; Carlson, Brian E.; Elson, Elliot L.; Genin, Guy M.

doi:10.1021/acsbiomaterials.6b00576

Cited by 18 publications

(17 citation statements)

References 53 publications

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“…235–236 In cases including cardiac tissue engineering, the electrical fields and their spatiotemporal modulation constitute a desired output rather than just an input to define composition. 50,237 From the perspective of tissue engineering, electrical fields have emerged as an effective tool to facilitate cell and tissue maturation in cardiac, 238–239 skeletal muscle, 240 neural, 241–242 and bone 243 tissue engineering. For instance, in cardiac tissue engineering, externally applied, pulsed electrical stimulation has been found to enhance the electrical communication between cardiomyocytes, synchronize their beating, and promote their maturation and mechanical output.…”

Section: The Cell Microenvironmentmentioning

confidence: 99%

Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment

et al. 2017

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The cell microenvironment has emerged as a key determinant of cell behavior and function in development, physiology, and pathophysiology. The extracellular matrix (ECM) within the cell microenvironment serves not only as a structural foundation for cells but also as a source of three-dimensional (3D) biochemical and biophysical cues that trigger and regulate cell behaviors. Increasing evidence suggests that the 3D character of the microenvironment is required for development of many critical cell responses observed in vivo, fueling a surge in the development of functional and biomimetic materials for engineering the 3D cell microenvironment. Progress in the design of such materials has improved control of cell behaviors in 3D and advanced the fields of tissue regeneration, in vitro tissue models, large-scale cell differentiation, immunotherapy, and gene therapy. However, the field is still in its infancy, and discoveries about the nature of cell-microenvironment interactions continue to overturn much early progress in the field. Key challenges continue to be dissecting the roles of chemistry, structure, mechanics, and electrophysiology in the cell microenvironment, and understanding and harnessing the roles of periodicity and drift in these factors. This review encapsulates where recent advances appear to leave the ever-shifting state of the art, and it highlights areas in which substantial potential and uncertainty remain.

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Section: The Cell Microenvironmentmentioning

confidence: 99%

Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment

et al. 2017

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“…Increased ECM stiffness has also been shown to influence CM differentiation and maturation. However, most of these earlier studies have focused on the electrotonic coupling between CMs and CFs with respect to substrate stiffness (17) or investigated the variation in conduction velocity in response to an increased population of nonmyocytes (i.e., CFs or CMFs) (18,19). In addition to electrotonic coupling, mechanical coupling also plays a major role in determining the efficiency of signal propagation between the myocardial cells (20,21).…”

Section: Introductionmentioning

confidence: 99%

Effect of Substrate Stiffness on Mechanical Coupling and Force Propagation at the Infarct Boundary

Nguyen

Nagarajan

Zorlutuna

2018

Biophysical Journal

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Heterogeneous intercellular coupling plays a significant role in mechanical and electrical signal transmission in the heart. Although many studies have investigated the electrical signal conduction between myocytes and nonmyocytes within the heart muscle tissue, there are not many that have looked into the mechanical counterpart. This study aims to investigate the effect of substrate stiffness and the presence of cardiac myofibroblasts (CMFs) on mechanical force propagation across cardiomyocytes (CMs) and CMFs in healthy and heart-attack-mimicking matrix stiffness conditions. The contractile forces generated by the CMs and their propagation across the CMFs were measured using a bio-nanoindenter integrated with fluorescence microscopy for fast calcium imaging. Our results showed that softer substrates facilitated stronger and further signal transmission. Interestingly, the presence of the CMFs attenuated the signal propagation in a stiffness-dependent manner. Stiffer substrates with CMFs present attenuated the signal $24-32% more compared to soft substrates with CMFs, indicating a synergistic detrimental effect of increased matrix stiffness and increased CMF numbers after myocardial infarction on myocardial function. Furthermore, the beating pattern of the CMF movement at the CM-CMF boundary also depended on the substrate stiffness, thereby influencing the waveform of the propagation of CM-generated contractile forces. We performed computer simulations to further understand the occurrence of different force transmission patterns and showed that cell-matrix focal adhesions assembled at the CM-CMF interfaces, which differs depending on the substrates stiffness, play important roles in determining the efficiency and mechanism of signal transmission. In conclusion, in addition to substrate stiffness, the degree and type of cell-cell and cell-matrix interactions, affected by the substrate stiffness, influence mechanical signal conduction between myocytes and nonmyocytes in the heart muscle tissue.

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“…Fibroblasts are responsible for the structural support and maintenance of the homogeneity of the cardiac tissue. During the fibrotic process, fibroblasts differentiate to myofibroblasts, cells that have been studied for their effect on reducing conduction velocity in the myocardium, promoting an arrythmogenic substrate [ 10 ].…”

Section: Fibrosismentioning

confidence: 99%

Atrial Fibrillation: Pathogenesis, Predisposing Factors, and Genetics

Sagris

Vardas

Theofilis

et al. 2021

IJMS

185

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Atrial fibrillation (AF) is the most frequent arrhythmia managed in clinical practice, and it is linked to an increased risk of death, stroke, and peripheral embolism. The Global Burden of Disease shows that the estimated prevalence of AF is up to 33.5 million patients. So far, successful therapeutic techniques have been implemented, with a high health-care cost burden. As a result, identifying modifiable risk factors for AF and suitable preventive measures may play a significant role in enhancing community health and lowering health-care system expenditures. Several mechanisms, including electrical and structural remodeling of atrial tissue, have been proposed to contribute to the development of AF. This review article discusses the predisposing factors in AF including the different pathogenic mechanisms, sedentary lifestyle, and dietary habits, as well as the potential genetic burden.

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Fibroblasts Slow Conduction Velocity in a Reconstituted Tissue Model of Fibrotic Cardiomyopathy

Cited by 18 publications

References 53 publications

Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment

Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment

Effect of Substrate Stiffness on Mechanical Coupling and Force Propagation at the Infarct Boundary

Atrial Fibrillation: Pathogenesis, Predisposing Factors, and Genetics

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