Molecule Associated With Poor Survival After Heart Attack – Detected

Heart failure is one of the deadly heart diseases, affecting 6.2 million Americans and mandates new therapies. It is an incurable disease with a staggering mortality rate of 40% within five years of diagnosis. Reducing the levels of a heart molecule, G protein-coupled receptor kinase 5 (GRK5) may promise a novel therapeutic strategy against heart failure as per a study at the Lewis Katz School of Medicine (LKSOM) at Temple University in new work, published in the journal Cardiovascular Research.

"Previous studies had found that GRK5 is elevated in patients with heart failure. Our new research, in mice that experienced a myocardial infarction (heart attack), shows that GRK5 overexpression is associated with physiological changes in the heart that decrease cardiac function", says Claudio de Lucia, MD, Ph.D., an associate scientist in the Center for Translational Medicine at LKSOM and lead author on the new study.

The study demonstrated the significant improvement in survival rate following heart attack in mice models.

GRK5 Levels in Heart Failure

The study 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.

It was found that raised levels of GRK5 in the heart were further known to be associated with increased recruitment of immune cells into damaged heart tissue and harmful inflammation. The combination of these factors thus reduced heart function and an influx of immune cells and inflammation that ultimately contributed to increased mortality in mice after a heart attack.

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The consequence of lower GRK5 levels in the heart was also investigated in a GRK5 knockout mouse model after securing a link between increased GRK5 expression, decreased heart function, and decreased survival in the weeks following a heart attack.

"After a heart attack, our 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. Highly selective drugs that block GRK5 are already available. Our next step is to test these agents in animal models of heart failure to determine their effect on cardiac function and survival", says, Dr. de Lucia.

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Thus targeting the abnormal levels and activity of GRK5 would imply a new drug class for heart failure, thereby supplementing significant and innovative benefits against heart disease. The study team further intends to concentrate on GRK5 inhibitors and knowing their effects in animals with heart disease.

Source-Medindia