Myofibroblasts impair myocardial impulse propagation by heterocellular connexin43 gap-junctional coupling through micropores

Aim: Composite population of myofibroblasts (MFs) within myocardial tissue is known to alter impulse propagation, leading to arrhythmias. However, it remains unclear whether and how MFs alter their propagation patterns when contacting cardiomyocytes (CMs) without complex structural insertions in the myocardium. We attempted to unveil the effects of the one-sided, heterocellular CM-MF connection on the impulse propagation of CM monolayers without the spatial insertion of MFs as an electrical or mechanical obstacle.Methods and results: We evaluated fluo8-based spatiotemporal patterns in impulse propagation of neonatal rat CM monolayers cultured on the microporous membrane having 8-μm diameter pores with co-culture of MFs or CMs on the reverse membrane side (CM-MF model or CM-CM model, respectively). During consecutive pacing at 1 or 2 Hz, the CM monolayers exhibited forward impulse propagation from the pacing site with a slower conduction velocity (θ) and a larger coefficient of directional θ variation in the CM-MF model than that in the CM-CM model in a frequency-dependent manner (2 Hz >1 Hz). The localized placement of an MF cluster on the reverse side resulted in an abrupt segmental depression of the impulse propagation of the upper CM layer, causing a spatiotemporally non-uniform pattern. Dye transfer of the calcein loaded in the upper CM layer to the lower MF layer was attenuated by the gap-junction inhibitor heptanol. Immunocytochemistry identified definitive connexin 43 (Cx43) between the CMs and MFs in the membrane pores. MF-selective Cx43 knockdown in the MF layer improved both the velocity and uniformity of propagation in the CM monolayer.Conclusion: Heterocellular Cx43 gap junction coupling of CMs with MFs alters the spatiotemporal patterns of myocardial impulse propagation, even in the absence of spatially interjacent and mechanosensitive modulations by MFs. Moreover, MFs can promote pro-arrhythmogenic impulse propagation when in face-to-face contact with the myocardium that arises in the healing infarct border zone

Induction of hepatocyte growth factor production in human dermal fibroblasts and their proliferation by the extract of bitter melon pulp

Hepatocyte growth factor (HGF) is useful as a potential therapeutic agent for hepatic and renal fibrosis and cardiovascular diseases through inducing proliferation of epithelial and endothelial cells. HGF inducers may also be useful as therapeutic agents for these diseases. However, there have been no reports on induction of HGF production by plant extracts or juices. An extract of bitter melon (Momordica charantia L.) pulp markedly induced HGF production. There was a time lag of 72 h before induction of HGF production after the extract addition. Its stimulatory effect was accompanied by upregulation of HGF gene expression. Increases in mitogen-activated protein kinases (MAPKs) were observed from 72 h after the extract addition. Inhibitors of MAPKs suppressed the extract-induced HGF production. The extract also stimulated cell proliferation. Both activities for induction of HGF production and cell proliferation were eluted together in a single peak with 14,000 Da on gel filtration. The results indicate that bitter melon pulp extract induced HGF production and cell proliferation of human dermal fibroblasts and suggest that activation of MAPKs is involved in the HGF induction. Our findings suggest potential usefulness of the extract for tissue regeneration and provide an insight into the molecular mechanism underlying the wound-healing property of bitter melon

Characteristics of soft x-ray emissions from Au plasmas generated with various driving laser pulse durations

X-ray microscope using water window X-rays (2.3-4.4 nm) emitted from laser plasmas enables us to observe nanoscale structures of living cells. For higher spatial resolution without blurring, we need bright X-ray source with a pulse duration of less than a few nanosecond. As a promising X-ray source, we have focused on laser produced gold plasmas that emit continuum radiation in water-window wavelengths. In this study, by using Nd-YAG laser systems (1064 nm) with pulse durations of 7 ns, 400 ps and 10 ps, characteristics of the laser plasmas were investigated. The target with a thickness of 0.3 mm was irradiated by the laser beams focused using a convex lens (100 mm). For spatial resolved X-ray measurement, a grazing incidence spectrometer (?at ?eld grating, 2400 grooves/mm) with a toroidal mirror was used. A pinhole camera with an aperture of 10 ?m observed 2D plasma emission image. Two photodetectors were installed to measure the X-ray pulse duration and its energy with respect to the laser incident angle. Compared with these measurements, dependence of the plasma properties on laser pulse duration was examined. We also evaluated the conversion e?ciency from laser to water-window X-rays.DPP19 Meeting of The American Physical Societ

Observation of water-window soft x-ray emission from laser-produced Au plasma under optically thin condition

We present a systematic approach how to charactorize the dynamics of a laser-produced Au plasma, generated with a commercial Joule-class laser system. By means of our diagnostic methods, we identify the dominant ionic species within the water-window spectral region, as well as the radiated energy, the x-ray emission duration and the total dimensions of the x-ray source. We present additional analysis through radiation hydrodynamic simulations to provide details about the electron temperature and density profiles and further show that the plasma exhibits nearly 20% self-absorption, while the electron temperature is limited to 400 eV. A comparison with the experimental data further allows us to verify the applied numerical code

Observation of keV X-ray emitted from laser produced Au plasmas by using a crystal spectrometer

X-ray emitted by a laser generated plasma has various applications. Serious issue to be solved is thatthe energy conversion e?ciency from the laser to X-ray is quite low. Recently, it was found that the X-ray emitted by the laser produced Auplasma increases under nitrogen atmospheres. In particular, the intensity of the water window soft X-ray (2.4-4.4 nm) increases approximately ten times. In order to elucidate this enhancement mechanism of X-ray, we have measured soft X-ray spectra from Au plasma in the wavelength of 1-7 nm so far. Recently, we fabricated a TAP crystal spectrometer to observe the photons over 1 keV region (1.0-1.9 eV), which provides useful information of plasma temperature. As a detector, an imaging plate(IP) was used. Titanium ?lters was also used to block out-of-band emission. As a result, continuum spectra attributed unresolved transition arrays (UTAs) was observed from the Au laser plasma. This spectral profile was compared with the Star2D hydrodynamic code.DPP19 Meeting of The American Physical Societ