Q58005444
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BACKGROUND: The ventricular trabeculae play a role, among others, in the impulse spreading in ectothermic hearts. Despite the morphological similarity with the early developing hearts of endotherms, this trabecular function in mammalian and avian embryos was poorly addressed. RESULTS: We simulated impulse propagation inside the looping ventricle and revealed delayed apical activation in the heart with inhibited trabecular growth. This finding was corroborated by direct imaging of the endocardial surface showing early activation within the trabeculae implying preferential spreading of depolarization along with them. Targeting two crucial pathways of trabecular formation (Neuregulin/ErbB and Nkx2.5), we showed that trabecular development is also essential for proper conduction patterning. Persistence of the slow isotropic conduction likely contributed to the pumping failure in the trabeculae-deficient hearts. CONCLUSIONS: Our results showed the essential role of trabeculae in intraventricular impulse spreading and conduction patterning in the early endothermic heart. Lack of trabeculae leads to the failure of conduction parameters differentiation resulting in primitive ventricular activation with consequent impact on the cardiac pumping function.
- MeSH
- neureguliny MeSH
- savci MeSH
- srdce * MeSH
- srdeční komory * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- blokáda Tawarova raménka * MeSH
- myši MeSH
- zobrazování pomocí barviva citlivého na potenciál MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
Endothelin (ET) signalling is essential for normal embryonic development. Disruption of this pathway leads to defects in the development of subsets of cranial and cephalic neural crest derivatives. Endothelin-converting enzyme 1 (ECE-1) is a ratelimiting step in the biosynthesis of ET-1. Recently, there has been considerable interest in the protective role of folic acid (FA) against congenital anomalies via increasing the expression of ET-1. We have tested whether FA supplementation can rescue craniofacial and cardiac defects observed in the ECE1-/- embryos. ECE1+/- mice were caged together to obtain litters containing embryos of all possible genotypes. The treatment group had the diet supplemented with 20 mg/kg of FA from the day of discovery of the vaginal plug. FA supplementation did not result in modified proportions of the genotypes, indicating no rescue of the embryonic mortality. There was also no effect on the litter size. Craniofacial and cardiac defects were likewise identical in the ECE1-/- embryos of both groups. There was a mild but significant reduction in the embryo size in wild-type and heterozygous FA-supplemented embryos, and there were haemorrhages in the wild-type supplemented embryos at ED14.5. Expression of ET receptor A detected by immunohistochemistry was up-regulated in the ECE1-/- embryos, but FA supplementation had no effects on the distribution of staining intensity. We conclude that FA is not able to rescue the phenotype in this model, suggesting an alternative pathway for its action. These results also caution against indiscriminate use of dietary supplements in attempts to prevent congenital anomalies.
- MeSH
- aspartátové endopeptidasy nedostatek genetika metabolismus MeSH
- embryo savčí účinky léků MeSH
- genotyp MeSH
- imunohistochemie MeSH
- kyselina listová farmakologie MeSH
- metaloendopeptidasy nedostatek genetika metabolismus MeSH
- myši knockoutované MeSH
- myši MeSH
- potravní doplňky MeSH
- regulace genové exprese enzymů účinky léků MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The primary ring, a horseshoe-shaped structure situated between the left and right ventricle and connected superiorly to the atrioventricular canal, is the first specialized fast ventricular conduction pathway in the embryonic heart. It has been first defined immunohistochemically and is characterized as a region of slow myocyte proliferation. Recent studies have shown that it participates in spreading the ventricular electrical activation during stages preceding ventricular septation in the mouse, chick, and rat. Here we demonstrate its presence using optical mapping in chicks between embryonic days (ED) 3-5. We then tested the effects of hemodynamic unloading in the organ culture system upon its functionality. In ED3 hearts cultured without hemodynamic loading for 24 h, we observed a significant decrease in the percentage activated through the primary ring conduction pathway. A morphological examination revealed arrested growth, collapse, and elongation of the outflow tract and disorganized trabeculation. A similar reversal toward more primitive activation patterns was observed with culture between ED4 and ED5. This phenotype was completely rescued with the artificial loading of the ventricles with a droplet of silicone oil. We conclude that an appropriate loading is required during the early phases of the conduction system formation and maturation.
- MeSH
- elektrofyziologie MeSH
- fyziologický stres MeSH
- hemodynamika fyziologie MeSH
- imunohistochemie MeSH
- kardiomyocyty fyziologie MeSH
- kontrakce myokardu fyziologie MeSH
- kuřecí embryo MeSH
- převodní systém srdeční embryologie fyziologie MeSH
- silikonové oleje diagnostické užití MeSH
- srdeční komory MeSH
- srdeční síně MeSH
- zvířata MeSH
- Check Tag
- kuřecí embryo MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
