NF-κB signaling blockade by Bay 11-7085 during early cardiac morphogenesis induces alterations of the outflow tract in chicken heart

Nuclear factor kappa B (NF-kappa B) is a pleiotropic transcription factor implicated in the regulation of diverse morphologic cardiac alterations, for which the p50 and p65 subunits form the most prevalent dimeric form in the heart. NF-kappa B is inactivated by proteins of the I kappa B family, which trap it in the cytoplasm. It is not known whether NF-kappa B influences cardiac development. Objective: Here we investigated the role of NF-kappa B in regulating transcription in chicken heart morphogenesis. Specifically, we tested whether NF-kappa B activation is required for normal formation of the outflow tract (OFT) during a critical stage of heart development. Methods and results: We designed a reporter vector with kappa B binding sites for Rel family members in the promoter, upstream from the cDNA of Green Fluorescent Protein (GFP). This construct was injected directly into the developing heart of chicken embryos. NF-kappa B activation was subsequently inhibited by administration of the specific pharmacological agent Bay 11-7085. We found that forced NF-kappa B expression was associated with multiple congenital cardiac alterations of the OFT (mainly IVC, DORV and great arteries stenosis). Conclusion: These findings indicate that blockade of NF-kappa B induces apoptosis and is an important factor in the development of OFT during cardiogenesis. However, it remains unknown which members of the Rel family are relevant in this process.