• International Journal of Vascular Biomedical Engineering
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• 제3권1호
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• pp.23-29
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• 2005

We developed a three dimensional cardiac tissue model based on human cardiac cell and mono-domain approximation for action potential propagation. The human myocyte model proposed by ten Tusscher et al. (TNNP model) (2004) for cell electrophysiology and a mono-domain method for electric wave propagation are used to simulate the cardiac tissue propagation mechanism using a finite element method. To delineate non-homogeneity across cardiac tissue layer, we used three types of cardiac cell models. Ansiotropic effect of action potential propagation is also considered in this study. In this 3D anisotropic cardiac tissue with three cell layers, we generated a reentrant wave using S1-S2 protocol. Computational results showed that the reentrant wave was affected by the anisotropic properties of the cells. To test the reentrant wave under pathological state, we simulated a hypertopic model with non-excitable fibroblasts in stochastic manner. Compared with normal tissue, the hypertropic tissue result showed another center of reentrant wave, indicating that the wave pattern can be more easily changed from regular with a concentric focus to irregular multi-focused reentrant waves in case of patients with hypertrophy.

• 대한기계학회:학술대회논문집
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• 대한기계학회 2005년도 창립60주년 기념 추계 학술대회
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• pp.58.1-58.1
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• 2005

• BMB Reports
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• 제56권1호
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• pp.32-42
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• 2023

Heart disease is one of the major life-threatening diseases with high mortality and incidence worldwide. Several model systems, such as primary cells and animals, have been used to understand heart diseases and establish appropriate treatments. However, they have limitations in accuracy and reproducibility in recapitulating disease pathophysiology and evaluating drug responses. In recent years, three-dimensional (3D) cardiac tissue models produced using tissue engineering technology and human cells have outperformed conventional models. In particular, the integration of cell reprogramming techniques with bioengineering platforms (e.g., microfluidics, scaffolds, bioprinting, and biophysical stimuli) has facilitated the development of heart-on-a-chip, cardiac spheroid/organoid, and engineered heart tissue (EHT) to recapitulate the structural and functional features of the native human heart. These cardiac models have improved heart disease modeling and toxicological evaluation. In this review, we summarize the cell types for the fabrication of cardiac tissue models, introduce diverse 3D human cardiac tissue models, and discuss the strategies to enhance their complexity and maturity. Finally, recent studies in the modeling of various heart diseases are reviewed.

• 한국정밀공학회:학술대회논문집
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• 한국정밀공학회 2004년도 추계학술대회 논문집
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• pp.1176-1179
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• 2004

A new cell-cross bridge mechanics model is proposed to analyze the mechanics of heart muscle. Electrophysiology of a cardiac cell is numerically approximated using the previous model of human ventricular myocyte. Ion transports across cell membrane initiated by action potential induce excitation-contraction mechanism in the cell via cross bridge dynamics. Negroni and Lascano model (NL model) is employed to compute the tension of cross bridge closely related to ion dynamics in cytoplasm.

• 제어로봇시스템학회논문지
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• 제10권12호
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• pp.1164-1171
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• 2004

A new multi-scale simulation model is proposed to analyze heart mechanics. Electrophysiology of a cardiac cell is numerically approximated using the previous model of human ventricular myocyte. The ion transports across cell membrane initiated by action potential induce an excitation-contraction mechanism in the cell via cross bridge dynamics. Negroni and Lascano model (NL model) is employed to calculate the tension of cross bridge which is closely related to the ion dynamics in cytoplasm. To convert the tension on cell level into contraction force of cardiac muscle, we introduce a simple geometric model of ventricle with a thin-walled hemispheric shape. It is assumed that cardiac tissue is composed of a set of cardiac myocytes and its orientation on the hemispheric surface of ventricle remains constant everywhere in the domain. Application of Laplace law to the ventricle model enables us to determine the ventricular pressure that induces blood circulation in a body. A lumped parameter model with 7 compartments is utilized to describe the systemic circulation interacting with the cardiac cell mechanism via NL model and Laplace law. Numerical simulation shows that the ion transports in cell level eventually generate blood hemodynamics on system level via cross bridge dynamics and Laplace law. Computational results using the present multi-scale model are well compared with the existing ones. Especially it is shown that the typical characteristics of heart mechanics, such as pressure volume relation, stroke volume and ejection fraction, can be generated by the present multi-scale cardiovascular model, covering from cardiac cells to circulation system.

• 대한기계학회:학술대회논문집
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• 대한기계학회 2007년도 춘계학술대회B
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• pp.2941-2946
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• 2007

A model of the cardiovascular system coupling cell, hemodynamics and autonomic nervecontrol function is proposed for analyzing heart mechanics. We developed a comprehensive cardiovascular model with multi-physics and multi-scale characteristics that simulates the physiological events from membrane excitation of a cardiac cell to contraction of the human heart and systemic blood circulation and ultimately to autonomic nerve control. Using this model, we delineatedthe cellular mechanism of heart contractility mediated by nerve control function. To verify the integrated method, we simulated a 10% hemorrhage, which involves cardiac cell mechanics, circulatory hemodynamics, and nerve control function. The computed and experimental results were compared. Using this methodology, the state of cardiac contractility, influenced by diverse properties such as the afterload and nerve control systems, is easily assessed in an integrated manner.

• 대한기계학회:학술대회논문집
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• 대한기계학회 2007년도 춘계학술대회B
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• pp.2947-2950
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• 2007

A 3D human ventricular model is proposed to simulate an integrative analysis of heart physiology and blood hemodynamics. This consists of the models of electrophysiology of human cells, electric wave propagation of tissue, heart solid mechanics, and 3D blood hemodynamics. The 3D geometry of human heart is discretized to a finite element mesh for the simulation of electric wave propagation and mechanics of heart. In cellular level, excitations by action potential are simulated using the existing human model. Then the contraction mechanics of a whole cell is incorporated to the excitation model. The excitation propagation to ventricular cells are transiently computed in the 3D cardiac tissue using a mono-domain method of electric wave propagation in cardiac tissue. Blood hemodynamics in heart is also considered and incorporated with muscle contraction. We use a PISO type finite element method to simulate the blood hemodynmaics in the human ventricular model.

• International Journal of Molecular Medicine
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• 제43권6호
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• pp.2319-2328
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• 2019

Exosomes serve important functions in cell-to-cell communication and biological functions by serving as a delivery cargo shuttle for various molecules. The application of an improved delivery method for microRNAs (miRNAs/miRs) may enhance their potential as a therapeutic tool in cardiac diseases. Thus, the present study investigated whether human peripheral blood-derived exosomes may be used as a delivery cargo system for miRNAs, and whether the delivery of miR-21 using a human peripheral blood derived-exosome may influence the degree of remodeling following myocardial infarction (MI). In H9C2 and HL-1 cells, miR-21 expression was successfully regulated by treatment with human peripheral blood derived-exosomes loaded with an miR-21 mimic or inhibitor compared with untreated cells. In addition, the mRNA and protein expression levels of SMAD family member 7 (Smad7), phosphatase and tensin homolog (PTEN) and matrix metalloproteinase 2 (MMP2), which are involved in cardiac fibrosis, were associated with the uptake of miR-21 mimic- or inhibitor-loaded exosomes. Similarly, the in vivo mRNA and protein expression of Smad7, PTEN and MMP2 were altered following treatment with miR-21 mimic- or inhibitor-loaded exosomes. Furthermore, miR-21 mimic-loaded exosomes enhanced fibrosis, whereas miR-21 inhibitor-loaded exosomes reduced fibrosis in a mouse MI model. These results suggested that miRNA-loaded human peripheral blood derived-exosomes may be used as a therapeutic tool for cardiac diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제20권1호
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• pp.111-117
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• 2016

Vagal nerve activity has been known to play a crucial role in the induction and maintenance of atrial fibrillation (AF). However, it is unclear how the distribution and concentration of local acetylcholine (ACh) promotes AF. In this study, we investigated the effect of the spatial distribution and concentration of ACh on fibrillation patterns in an in silico human atrial model. A human atrial action potential model with an ACh-dependent $K^+$ current ($I_{KAch}$) was used to examine the effect of vagal activation. A simulation of cardiac wave dynamics was performed in a realistic 3D model of the atrium. A model of the ganglionated plexus (GP) and nerve was developed based on the "octopus hypothesis". The pattern of cardiac wave dynamics was examined by applying vagal activation to the GP areas or randomly. AF inducibility in the octopus hypothesis-based GP and nerve model was tested. The effect of the ACh concentration level was also examined. In the single cell simulation, an increase in the ACh concentration shortened $APD_{90}$ and increased the maximal slope of the restitution curve. In the 3D simulation, a random distribution of vagal activation promoted wavebreaks while ACh secretion limited to the GP areas did not induce a noticeable change in wave dynamics. The octopus hypothesis-based model of the GP and nerve exhibited AF inducibility at higher ACh concentrations. In conclusion, a 3D in silico model of the GP and parasympathetic nerve based on the octopus model exhibited higher AF inducibility with higher ACh concentrations.

• Journal of Ginseng Research
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• 제47권2호
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• pp.237-245
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• 2023

Background: Ginsenoside Rg2 (Rg2) has a variety of pharmacological activities and provides benefits during inflammation, cancer, and other diseases. However, there are no reports about the relationship between Rg2 and atherosclerosis. Methods: We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to detect the cell viability of Rg2 in vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs). The expression of inflammatory factors in HUVECs and the expression of phenotypic transformation-related marker in VSMCs were detected at mRNA levels. Western blot method was used to detect the expression of inflammation pathways and the expression of phenotypic transformation at the protein levels. The rat carotid balloon injury model was performed to explore the effect of Rg2 on inflammation and phenotypic transformation in vivo. Results: Rg2 decreased the expression of inflammatory factors induced by lipopolysaccharide in HUVECs-without affecting cell viability. These events depend on the blocking regulation of NF-κB and p-ERK signaling pathway. In VSMCs, Rg2 can inhibit the proliferation, migration, and phenotypic transformation of VSMCs induced by platelet derived growth factor-BB (PDGF-BB)-which may contribute to its anti-atherosclerotic role. In rats with carotid balloon injury, Rg2 can reduce intimal proliferation after injury, regulate the inflammatory pathway to reduce inflammatory response, and also suppress the phenotypic transformation of VSMCs. Conclusion: These results suggest that Rg2 can exert its anti-atherosclerotic effect at the cellular level and animal level, which provides a more sufficient basis for ginseng as a functional dietary regulator.