Nitrosative Stress and Cardiogenesis: Cardiac Remodelling Perturbs Embryonic Metabolome
Nitrosative stress because of hyperactive redox milieu is thought to be associated with decrease in bioavailability of nitric oxide and the subsequent defective cardiogenesis. The role of nitrosative stress in pathophysiology of the heart in adults has been studied for several decades; however, very few studies link the structural deformities in the heart with nitrosative stress. In this article, we give a detailed discussion of evidence of the impact of nitrosative stress during cardiogenesis and also the effect of following cardiac remodelling on the metabolism of the embryo. We highlight specifically the reactive nitrogen species (RNS)-mediated structural changes in the cardiac looping and predicted its consequences on embryonic metabolism using transcriptome analysis. In the present study, we used thalidomide as RNS inducer, which increases peroxynitrite and superoxide levels in the developing heart. The transcriptome analysis of thalidomide-treated embryos showed that the treatment affected severely the protein and fatty acid metabolism that consequently might lead to thalidomide-mediated heart defects in the embryo. To summarize, our data suggest that fatty acid metabolism, which is a critical metabolic pathway during heart development, is perturbed under an oxidative and nitrosative environment due to thalidomide treatment.
KeywordsNitrosative stress Congenital heart diseases Cardiogenesis Thalidomide Transcriptome Metabolome
This work was supported by a grant from University Grant Commission Faculty Recharge Programme (UGC-FRP) Government of India to SC. PK is thankful for the financial support from University Grant Commission-Senior Research Fellowship programme (UGC-SRF), Government of India. LS received financial support from the Department of Biotechnology-Senior Research Fellowship (DBT-SRF) programme, Government of India.
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