A team of scientists at the Baylor College of Medicine recently reported on a particular gene that, while vital for proper cardiac development, plays a major role in the pathology of dilated cardiomyopathy when overexpressed. The team found that suppressing this gene in mice models of heart failure led to a notably prolonged life. The study, titled “Increased COUP-TFII expression in adult hearts induces mitochondrial dysfunction resulting in heart failure” is available online in the journal Nature Communications.
“We knew that in heart failure patients there is a overexpression of the gene COUP-TFII,” said in a news release 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.”
Dr. Tsai and her fellow Baylor researchers discovered that the gene COUP-TFII determined gene expression in cellular mitochondria. When overexpressed, these power-house organelles produced excessive reactive oxygen species. This is normally a byproduct of mitochondrial function, but when generated excessively can damage cardiac cells and eventually lead to organ 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.”
The researchers are confident that the study’s findings can open doors to unexplored approaches to treating dilated cardiomyopathy, a condition characterized by an abnormal heart muscle. Further studies are still necessary to establish such approaches, but the eventual goal for future treatment research is to find a way to inhibit excessive COUP-TFII expression.
“It was thought that the gene expression was a consequence of dilated cardiomyopathy, but we have found that it is part of the cause,” concluded Dr. Ming-Jer Tsai. “This gives us a target for further research needed before clinical application.”