About 6.2 million Americans suffer from heart failure, an incurable disease with a staggering mortality rate—some 40% of patients die within five years of diagnosis.
Heart failure is one form of heart disease for which new therapies are desperately needed.
In a new study, researchers found the poor survival after a heart attack is linked to excess levels of signaling protein in the heart.
They found that GRK5 over-expression is linked to physiological changes in the heart that decrease cardiac function.
They also showed that reducing the protein GRK5 levels can strongly improve survival following a heart attack.
The research was conducted by scientists at Temple University.
Previous studies had found that GRK5 is elevated in patients with heart failure.
Too much GRK5 in the heart was further linked to increased recruitment of immune cells into damaged heart tissue and harmful inflammation.
The combination of these factors—reduced heart function and an influx of immune cells and inflammation—ultimately contributed to increased death after a heart attack.
In the study, the team examined GRK5 levels in the heart eight weeks after mice experienced a heart attack.
By that time, animals had developed a condition known as post-ischemic heart failure, in which heart function declines over time owing to the reduced blood supply.
Tissue damage that impairs circulation in the heart ultimately starves heart cells of the oxygen and nutrients they need to keep the heart working.
After establishing a link between increased GRK5 expression, decreased heart function, and decreased survival in the weeks following a heart attack, the researchers explored the effect of manipulating GRK5 to lower its levels in the heart.
They found after a heart attack, GRK5 knockout mice had much better heart function and better survival curves compared to wild-type mice with normal GRK5.
This raises the possibility that GRK5 inhibition may be a viable therapeutic strategy in human patients, as well.
The team says highly selective drugs that block GRK5 are already available.
One author of the study is Claudio de Lucia, MD, Ph.D.
The study is published in Cardiovascular Research.
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