Del Olmo-Turrubiarte A, Sánchez-Gómez C, López-Martínez B, Contreras-Ramos A

Language: Spanish
References: 23
Page: 124-132
PDF size: 428.90 Kb.

ABSTRACT

Background. Serious ventricular septal defects associated with ventricular hypoplasia and other hyperplasias or total absence of the interventricular septum (IVS) are usually incompatible with embryonic and fetal life. Despite the importance of these cardiac diseases, their causes are not yet known. Using in vivo labeling in the chick embryo, the importance of ventricular trabeculation was confirmed in IVS morphogenesis. Using knockout mice and retrovirus in birds, it was determined that lack of function of neuregulin 1 (NRG1) or its ErbB receptors not only causes deficient differentiation of ventricular myocytes and poor formation of trabeculae, but also determines premature death of the embryos. Based on this background, the aim of this study was to determine the actual role of NRG1 in early trabeculogenesis and its importance in proliferation and apoptosis regulation.
Methods. An embryonic chicken heart organ culture system at the age prior to the beginning of the trabeculogenesis process was established. Endogenous activity of NRG1 was inhibited in the organ cultures that were then stimulated with NRG1 at different concentrations. Myocyte proliferation was determined using the proliferating cell nuclear antigen and apoptosis with LysoTracker.
Results. Fetal bovine serum promotes proliferation but negatively impacts trabeculogenesis. Addition of NRG1 at low concentrations and for short periods of incubation does not induce trabeculogenesis. In contrast, average NRG1 concentrations and cultivation periods not exceeding 24 h have a positive effect on the onset of this process. This also promotes myocardial proliferation but avoids apoptosis. Higher concentrations of NRG1 possibly cause a molecular imbalance that favors untidy proliferation but not trabeculogenesis.
Conclusions. Understanding of the role of NRG1 on ventricular trabeculogenesis provides valuable information for the molecular pathways also involved in IVS development. This information is essential for understanding the origin of serious ventricular septal defects.

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