Modulation of cardiac myocyte beating rate and hypertrophy by cardiac fibroblasts isolated from neonatal rat ventricle.

Orita, Hiroyuki; Fukasawa, Manabu; Hirooka, Shigeki; Uchino, Hideaki; Fukui, Kana; M, Washio

doi:10.1253/jcj.57.912

Cited by 28 publications

(19 citation statements)

References 19 publications

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“…They play an important physiological role in regulating the activities of myocytes in vivo. Cardiac fibroblasts can modulate the beating frequency of myocytes (27), alter the hypertrophic response of myocytes to growth factors (30) and to mechanical load (38), and change the distribution of extracellular matrix components to influence cardiac development (4) and remodeling (26). The physiological importance of the nonmyocytes in the myocardium cannot be overstated.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of fibroblast proliferation in cardiac myocyte cultures by surface microtopography

Boateng¹,

Hartman²,

Ahluwalia³

et al. 2003

American Journal of Physiology-Cell Physiology

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Cardiac myocyte cultures usually require pharmacological intervention to prevent overproliferation of contaminating nonmyocytes. Our aim is to prevent excessive fibroblast cell proliferation without the use of cytostatins. We have produced a silicone surface with 10-microm vertical projections that we term "pegs," to which over 80% of rat neonatal cardiac fibroblasts attach within 48 h after plating. There was a 50% decrease in cell proliferation by 5 days of culture compared with flat membranes (P < 0.001) and a concomitant 60% decrease (P < 0.01) in cyclin D1 protein levels, suggesting a G1/S1 cell cycle arrest due to microtopography. Inhibition of Rho kinase with 5 or 20 microM Y-27632 reduced attachment of fibroblasts to the pegs by over 50% (P < 0.001), suggesting that this signaling pathway plays an important role in the process. Using mobile and immobile 10-microm polystyrene spheres, we show that reactive forces are important for inhibiting fibroblast cell proliferation, because mobile spheres failed to reduce cell proliferation. In primary myocyte cultures, pegs also inhibit fibroblast proliferation in the absence of cytostatins. The ratio of aminopropeptide of collagen protein from fibroblasts to myosin from myocytes was significantly reduced in cultures from pegged surfaces (P < 0.01), suggesting an increase in the proportion of myocytes on the pegged surfaces. Connexin43 protein expression was also increased, suggesting improved myocyte-myocyte interaction in the presence of pegs. We conclude that this microtextured culture system is useful for preventing proliferation of fibroblasts in myocyte cultures and may ultimately be useful for tissue engineering applications in vivo.

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Section: Discussionmentioning

confidence: 99%

Inhibition of fibroblast proliferation in cardiac myocyte cultures by surface microtopography

Boateng¹,

Hartman²,

Ahluwalia³

et al. 2003

American Journal of Physiology-Cell Physiology

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“…Following the method proposed by Orita et al (1993), cardiac myocytes were prepared from 1 to 3-day-old neonatal Wistar rat ventricles that were removed after decapitation. The ventricles were rinsed in a 25 mM HEPES buffered minimum salt solution (MSS) to remove contaminating blood cell components, and then minced with scissors into fragments to be digested with 0.1% collagenase (Wako Chemical, Tokyo) in MSS at 37°C for 60 min.…”

Section: Cardiac Myocyte Culturementioning

confidence: 99%

Changes in the fluctuation of interbeat intervals in spontaneously beating cultured cardiac myocytes: experimental and modeling studies

Yamauchi

Harada

Kikuchi

2002

Biological Cybernetics

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Isolated and cultured neonatal cardiac myocytes contract spontaneously and cyclically, and have the properties of a non-linear oscillator. In this study, we have analyzed the relationship between the fluctuation of contraction rhythm of spontaneously beating cultured cardiac myocytes, and the coupling strength among them. The coefficient of variation of contraction intervals increased transiently in the early stages of incubation, and then decreased almost monotonically with time. The contraction rhythm of the myocytes became synchronized in the late stage of the culture. The day on which synchronization occurred almost coincided with the day when the coefficient of variation reached its lowest value. In addition, we have performed a mathematical analysis using interacting Bonhoeffer-van der Pol oscillators to clarify the mechanisms underlying the changes in the fluctuation of contraction rhythm with time. As the coupling strength among oscillators increased, the coefficient of variation of oscillation periods increased temporarily, but then decreased rapidly when the oscillators showed synchronization. These results suggest that the changes in the fluctuation of beating rhythm result from the increase in strength of electrical coupling among spontaneously beating cardiac myocytes.

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“…Thus, it is highly probable that monolayers of NRVMs are heterogeneous networks of these two cell types. The spontaneous beating rate in these cultures is reportedly modulated by plating density [13]; however, the specific effects of PM cell density and spatial distribution on confluent monolayer spontaneous frequency are still unknown.…”

Section: Introductionmentioning

confidence: 99%

Multicellular automaticity of cardiac cell monolayers: effects of density and spatial distribution of pacemaker cells

et al. 2014

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The biological pacemaker approach is an alternative to cardiac electronic pacemakers. Its main objective is to create pacemaking activity from added or modified distribution of spontaneous cells in the myocardium. This paper aims to assess how automaticity strength of pacemaker cells (i.e. their ability to maintain robust spontaneous activity with fast rate and to drive neighboring quiescent cells) and structural linear anisotropy, combined with density and spatial distribution of pacemaker cells, may affect the macroscopic behavior of the biological pacemaker. A stochastic algorithm was used to randomly distribute pacemaker cells, with various densities and spatial distributions, in a semi-continuous mathematical model. Simulations of the model showed that stronger automaticity allows onset of spontaneous activity for lower densities and more homogeneous spatial distributions, displayed more central foci, less variability in cycle lengths and synchronization of electrical activation for similar spatial patterns, but more variability in those same variables for dissimilar spatial patterns. Compared to their isotropic counterparts, in silico anisotropic monolayers had less central foci and displayed more variability in cycle lengths and synchronization of electrical activation for both similar and dissimilar spatial patterns. The present study established a link between microscopic structure and macroscopic behavior of the biological pacemaker, and may provide crucial information for optimized biological pacemaker therapies.

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Modulation of cardiac myocyte beating rate and hypertrophy by cardiac fibroblasts isolated from neonatal rat ventricle.

Cited by 28 publications

References 19 publications

Inhibition of fibroblast proliferation in cardiac myocyte cultures by surface microtopography

Inhibition of fibroblast proliferation in cardiac myocyte cultures by surface microtopography

Changes in the fluctuation of interbeat intervals in spontaneously beating cultured cardiac myocytes: experimental and modeling studies

Multicellular automaticity of cardiac cell monolayers: effects of density and spatial distribution of pacemaker cells

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