Before birth, cardiac muscle cells use energy generated by breaking down glucose. Immediately after birth, they rapidly switch to breaking down fatty acids. This switch is hindered in hypertrophied newborn hearts. In order to investigate how this process takes place at the molecular level, scientists at the Hokkaido University cardiologist Arata Fukushima, along with a team of the University of Alberta have conducted a study where they discovered a metabolic process that provides heart muscle with energy fails to mature in newborns with thickened heart walls.
Scientists examined the heart tissue of 84 infants who had experienced medical procedure for congenital heart disease. Numerous patients with the illness create thickened heart walls, or hypertrophy, which can prompt fatal heart failure even after the medical procedure.
Scientists next analyzed the biopsy samples taken from normal and thickened right ventricular walls. They found that two catalysts engaged in the fatty acid breakdown, called LCAD and βHAD, were ‘hyperacetylated’ in non-hypertrophied right ventricles. This means that large amounts of acetyl groups were added to the enzyme proteins, increasing their activity levels. This, in turn, led to increased fatty acid metabolism.
In hypertrophied hearts, these two enzymes were not hyperacetylated, prompting diminished unsaturated fat in these infants. Scientists recognized the diminished action of an acetylation promoting gene, called gcn5l1, in hypertrophied hearts.
At the point when the group investigated cultured hypertrophy-like cardiovascular muscle cells, they found that killing the gcn5l1 quality prompted diminished acetylation of LCAD and βHAD, and a lessened unsaturated fat oxidation in the cells. In addition, the cells lacking gcn5l1 shaped thicker muscle strands contrasting with typical cells.
Arata Fukushima, a cardiologist at Hokkaido University said, “Our findings show that acetylation of metabolic enzymes plays an important role in controlling the dramatic changes in energy metabolism that occur in newborn hearts immediately after birth. The findings also show how hypertrophy can perturb this process by delaying the maturation of fatty acid metabolism, which compromises the ability of the newborn heart to generate energy. Developing drugs that enhance acetylation of the metabolic enzymes could help treat patients with hypertrophy.”
The study is published in The Journal of Clinical Investigation Insight.