Developmental Changes in Ventricular Diastolic Function Correlate With Changes in Ventricular Myoarchitecture in Normal Mouse Embryos

Ishiwata, Takahiro; Nakazawa, Makoto; Pu, William T.; Tevosian, Sergei G.; Izumo, Seigo

doi:10.1161/01.res.0000100389.57520.1a

Cited by 79 publications

(79 citation statements)

References 43 publications

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“…In human fetuses, this same transition was observed as early as 8 weeks of gestation (Yagel et al 2003;van Splunder et al 1996). As a small Ewave could be detected in mouse embryos as early as E9.5 using a 20-MHz zero-cross pulsed Doppler velocimeter (Ishiwata et al 2003), it's likely the amplitude of the E-wave normally ramps up at E11.5. The E/A ratio was observed to increase as development progressed, which may be indicative of an overall increase in ventricular compliance in fetal mice (Gui et al 1996;Zhou et al 2003;Spurney et al 2004).…”

Section: Discussionmentioning

confidence: 71%

Cardiovascular Assessment of Fetal Mice by In Utero Echocardiography

Leatherbury

Tian

et al. 2008

Ultrasound in Medicine & Biology

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To establish a developmental profile of fetal mouse cardiovascular parameters, we analyzed a large body of ultrasound measurements obtained by in utero echocardiography of C57BL/6J fetal mice from embryonic day 12.5 to 19.5 (term). Measurements were obtained using 2D, spectral Doppler and M-mode imaging with standard clinical cardiac ultrasound imaging planes. As these studies were conducted as part of a large scale mouse mutagenesis screen, stringent filtering criteria were used to eliminate potentially abnormal fetuses. Our analysis showed heart rate increased from 190 to 245 bpm as the mouse fetus grew from 8 mm at embryonic day 12.5 to 18.7 mm at term. This was accompanied by increases in peak outflow velocity, E-wave, E/A ratio and ventricular dimensions. In contrast, the A-wave, myocardial performance index and isovolemic contraction time decreased gradually. Systolic function remained remarkably stable at 80% ejection fraction. Analysis of intra and interobserver variabilities showed these parameters were reproducible, with most comparing favorably to clinical ultrasound measurements in human fetuses. A comprehensive database was generated comprising 23 echocardiographic parameters delineating fetal mouse cardiovascular function from embryonic day 12.5 to term. This database can serve as a standard for evaluating cardiovascular pathophysiology in genetically altered and mutant mouse models.

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Section: Discussionmentioning

confidence: 71%

Cardiovascular Assessment of Fetal Mice by In Utero Echocardiography

Leatherbury

Tian

et al. 2008

Ultrasound in Medicine & Biology

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“…As we reported previously, the ventricular trabecular myocardium, which is suggested to have a higher passive compliance because of its lower expression levels of SERCA2A, RyR, and NCX than the compact myocardium, proliferates rapidly from the early to mid-embryonic stages, whereas the compact myocardium remains as a thin layer. 6 The rapid proliferation of myocytes of the trabecular myocardium possibly accounted for the slower decay of Ca 2+ transients, indicating a stiffer property of the ventricular myocardium at ED 14.5 than at ED 10.5.…”

Section: Developmental Changes Of Ca 2+ Homeostasis and Ventricular Dmentioning

confidence: 97%

“…Previously, we demonstrated that the ventricular myocardium of a mouse embryo is stiffer than that of an adult mouse, and that diastolic function develops in proportion to the thickness of a compact myocardium. 6 A compact myocardium expresses higher levels of SERCA2A, RyR, and NCX than a trabecular myocardium, 7 suggesting that the compact myocardium is better adapted to relaxation than the trabecular myocardium. In addition to the proliferation of myocytes of a compact myocardium in late embryonic hearts, the developmental changes to rapid decay of Ca 2+ transients well account for the accelerated development of ventricular diastolic function during the late embryonic stages.…”

Section: Developmental Changes Of Ca 2+ Homeostasis and Ventricular Dmentioning

confidence: 99%

“…[2][3][4][5] In embryonic mice, we showed that the increase in thickness of a compact myocardium tightly regulates ventricular diastolic function. 6 A compact myocardium starts to increase in thickness in the late embryonic stages and expresses higher levels of sarcoplasmic Ca 2+ -ATPase (SERCA) 2A, ryanodine receptor (RyR) 2, and Na + /Ca 2+ exchanger (NCX) than a trabecular myocardium. 7 Aside from morphological changes, the E-C coupling in immature cardiac myocytes is also different from that in mature cardiac myocytes.…”

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confidence: 99%

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Fetal and Neonatal Development of Ca2+ Transients and Functional Sarcoplasmic Reticulum in Beating Mouse Hearts

Kawamura

Ishiwata

Takizawa

et al. 2010

Circ J

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Background: It is generally accepted that Ca 2+ -induced Ca 2+ release is not the predominant mechanism during embryonic stages. Most studies have been conducted either on primary cultures or acutely isolated cells, in which an apparent reduction of ryanodine receptor density and alterations in the cell shape have been reported. The aim of the present study was to investigate developmental changes in Ca 2+ transients using whole hearts of mouse embryos and neonates. Methods and Results:Fluo-3 fluorescence signals from stimulated whole hearts were detected using a photomultiplier and stored as Ca 2+ transients. The upstroke and decay of Ca 2+ transients became more rapid from the late embryonic stages to the neonatal stage. After thapsigargin application (an inhibitor of the sarcoplasmic Ca 2+ -ATPase [SERCA]), time to 50% relaxation (T50) of Ca 2+ transients was significantly prolonged. There were no significant changes in T50 after Ru360 application (an inhibitor of mitochondrial Ca 2+ uniporter). The rate of increase in the amplitude of Ca 2+ transients after caffeine application became larger during developmental stages.Conclusions: Ca 2+ homeostasis developmentally changes from a slow rise and decay of Ca 2+ transients to rapid kinetics after the mid-embryonic stage. SERCA began to contribute significantly to Ca 2+ homeostasis at early embryonic stages and sarcoplasmic reticulum Ca 2+ contents increased from embryonic to neonatal stages, whereas mitochondrial Ca 2+ uptake did not contribute to Ca 2+ transients on a beat-to-beat basis. (Circ J 2010; 74: 1442 -1450

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“…Significantly, this complex developmental program requires the coordinated expansion of the different populations of cardiac progenitors and early CMs to allow for a greater than 300-fold increase in muscle mass (von Gise et al, 2012). This increase of mass has to be tightly linked to complex morphological changes (Ishiwata et al, 2003;von Gise et al, 2012). Work from a number of laboratories over several decades has shown that cardiomyocytes in the compact myocardium have a significantly higher proliferation rate than cardiomyocytes in the trabecular myocardium during normal cardiac development.…”

Section: Introductionmentioning

confidence: 99%

Wnt/β-catenin signaling directs the regional expansion of first and second heart field-derived ventricular cardiomyocytes

et al. 2013

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SUMMARYIn mammals, cardiac development proceeds from the formation of the linear heart tube, through complex looping and septation, all the while increasing in mass to provide the oxygen delivery demands of embryonic growth. The developing heart must orchestrate regional differences in cardiomyocyte proliferation to control cardiac morphogenesis. During ventricular wall formation, the compact myocardium proliferates more vigorously than the trabecular myocardium, but the mechanisms controlling such regional differences among cardiomyocyte populations are not understood. Control of definitive cardiomyocyte proliferation is of great importance for application to regenerative cell-based therapies. We have used murine and human pluripotent stem cell systems to demonstrate that, during in vitro cellular differentiation, early ventricular cardiac myocytes display a robust proliferative response to β-cateninmediated signaling and conversely accelerate differentiation in response to inhibition of this pathway. Using gain-and loss-of-function murine genetic models, we show that β-catenin controls ventricular myocyte proliferation during development and the perinatal period. We further demonstrate that the differential activation of the Wnt/β-catenin signaling pathway accounts for the observed differences in the proliferation rates of the compact versus the trabecular myocardium during normal cardiac development. Collectively, these results provide a mechanistic explanation for the differences in localized proliferation rates of cardiac myocytes and point to a practical method for the generation of the large numbers of stem cell-derived cardiac myocytes necessary for clinical applications.

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Developmental Changes in Ventricular Diastolic Function Correlate With Changes in Ventricular Myoarchitecture in Normal Mouse Embryos

Cited by 79 publications

References 43 publications

Cardiovascular Assessment of Fetal Mice by In Utero Echocardiography

Cardiovascular Assessment of Fetal Mice by In Utero Echocardiography

Fetal and Neonatal Development of Ca2+ Transients and Functional Sarcoplasmic Reticulum in Beating Mouse Hearts

Wnt/β-catenin signaling directs the regional expansion of first and second heart field-derived ventricular cardiomyocytes

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