Too much of a good thing isn’t always best. A gene that plays an important role in heart development has been found to also play a role in dilated cardiomyopathy (a heart muscle malfunction) when overexpressed. Researchers at Baylor College of Medicine say suppressing the gene in heart failure mouse models can prolong life.
The findings appear in the current edition of Nature Communications.
“We knew that in heart failure patients there is an overexpression of the gene COUP-TFII,” said Dr. Sophia Tsai, professor of molecular and cellular biology at Baylor and co-corresponding author on the study. “Using mouse models with overexpression of COUP-TFII with a similar level of what we observed in patients, we saw a rapid decline in health. So we looked into why this happens.”
Focusing on this gene, Tsai and her colleagues also found that COUP-TFII plays a role in mitochondrial gene expression. Mitochondria are organelles in the cell that are responsible for energy production. When levels of the COUP-TFII were overexpressed it created an overload of reactive oxygen, a normal byproduct of mitochondria, which damages the cell causing heart failure.
“When the system functions properly, COUP-TFII expression is very low. But when its expression is induced in heart disease patients, the mitochondria function is disrupted, which damages the heart,” said Dr. Ming-Jer Tsai, professor of molecular and cellular biology at Baylor and co-corresponding author on the study. “So we found that if we suppress this gene in mouse models we could prolong life.”
Both Tsais believe that this finding eventually will lead to a possible treatment for patients with dilated cardiomyopathy. More studies are needed but the goal is to find an inhibitor for COUP-TFII.
“It was thought that the gene expression was a consequence of dilated cardiomyopathy, but we have found that it is part of the cause,” said Ming-Jer Tsai. “This gives us a target for further research needed before clinical application.”
Others who took part in the study include lead author San-Pin Wu, formerly with Baylor and currently with the Adrienne Helis Malvin Medical Research Foundation in New Orleans; Chung-Yang Kao, Leiming Wang, Chad J. Creighton, Taraka R. Donti, Brett H. Graham, Hugo J. Bellen, all with Baylor; Jin Yan and Ching-Pin Chang, both with Indiana University School of Medicine; Romain Harmancey, Hernan G. Vasquez, and Heinrich Taegtmeyer, all with The University of Texas Medical School at Houston.
Funding for this research came from grants from NIH DK59820 and HL114539, DK45641, HL061483, NCI P30 CA125123 and K99 HL112952.