A study conducted in Japan has identified a receptor on heart cells that may be involved in chronic heart failure.
The researchers hope their research might pave the way for better, more effective treatment.
Chronic heart failure is a condition in which the heart no longer pumps blood as efficiently as it should.
It can develop due to a number of conditions, such as high blood pressure, diabetes, or coronary heart disease (in which the arteries of the heart are narrowed).
As chronic heart failure progresses over time, the heart attempts to compensate for the damage in a number of ways – by growing larger, for example.
However, the heart gradually loses the battle, and, eventually, it is no longer able to pump enough oxygen-rich blood around the body.
According to the Centers for Disease Control and Prevention (CDC), people in the United States have heart failure. One in nine deaths in 2009 had heart failure as a contributing cause.
Globally, an estimated 20 million people are affected.
Among the risk factors for heart failure are diabetes and obesity. As the prevalence of both of these conditions steadily rises across the U.S., heart failure cases are likely to follow suit.
A study carried out at Nagoya University School of Medicine in Japan looked at the influence of specific receptors on the surface of heart cells.
The results were published today in The Journal of Experimental Medicine.
Heart failure and Crhr2
Headed up by Mikito Takefuji, the research team was particularly interested in a signaling protein called corticotropin releasing hormone receptor 2 (Crhr2).
This receptor is found on the surface of heart muscle cells, or cardiomyocytes.
The researchers showed that levels of Crhr2 in both mice and humans with heart failure.
Crhr2 is a G protein-coupled receptor. Part of a large family of receptors, they come in a variety of forms and are found on the membranes of many cell types.
They detect specific molecules outside of the cell and then trigger activity within the cell, allowing external signals to influence cellular activity.
In the case of Crhr2, a molecule called urocortin 2 (Ucn2) activates the receptor and alters cardiomyocyte function.
Earlier studies have shown that when Crhr2 is triggered by Ucn2, signal pathways are switched on that result in the expression of genes that can impair heart function.
Infusion of Ucn2 in healthy humans to increase a number of cardiac measures, including output, heart rate, and left ventricle ejection fraction (that is, how much blood the left ventricle pumps out).
These changes, it is thought, are an attempt by the heart to compensate for the failing organ.
The future of heart failure medication
In the current experiment, the researchers wanted to understand what might happen if the activity between Ucn2 and Crhr2 was minimized, including whether it could impact heart health.
They found that mice with no Crhr2 were protected against the effects of Ucn2 and “were resistant to developing heart failure.”
Similarly, when the team used a molecule that inhibits Crhr2’s action, cardiac function was maintained, and damage to the heart was minimized.
“Our results suggest that constitutive Crhr2 activation causes cardiac dysfunction and that Crhr2 blockade could be a promising therapeutic strategy for patients with chronic heart failure,” said Takefuji.
G protein-coupled receptors are a well-researched family of receptors and are relatively easy to target with drugs – so much so, that a range of potential drugs already exist.
In fact, an estimated of all prescription pharmaceuticals currently target G protein-coupled receptors.
Although there are medications that help to treat heart failure, there is no cure. Around half of patients with chronic heart failure die within five years of their diagnosis.