Wolfgang RottbauerOver the course of a lifetime, the heart is known to pump some 250 million liters of blood through the body. In the order to do this, the muscle fibers of the heart may perhaps have to be extremely durable.

Scientists from Heidelberg University Hospital are believed to have found a protein that is responsible for the stability of the smallest muscular unit called the sarcomere. They proved that mutations of this protein could be the cause of a latest type of heart failure.

Primary heart muscle disease with reduced cardiac pump function leading to dilated cardiomyopathy seems to be one of the most common causes of chronic heart failure. Dilated cardiomyopathy refers to enlargement of the heart chambers.

It was estimated that nearly six new cases per 100,000 people happen every year while approximately 20 percent of these cases are genetic. The heart disease supposedly deteriorates cardiac cells and the heart can no more pump efficiently. This may in turn lead to dilation of the cardiac chambers.

Muscle activity seems to occur in the smallest unit of muscle fiber, the sarcomere. In the presence of a suitable stimulus, actin and myosin filaments appear to interact and contract the muscle. These movable elements are believed to have been anchored in what are known as Z-disks. Additionally, with every heartbeat, enormous forces could possibly act on the Z-disks.

Lead author of the study, Dr. Wolfgang Rottbauer, vice chair of the Department of Medicine III at Heidelberg University Hospital cooperated with other scientists within the National Genome Research Network (NGFN).They were noted to have analyzed the genetic material of affected patients and verified a mutated Z-disk protein in 9 of 1000 participants.

“In our studies of zebrafish, we discovered a protein that is needed to stabilize the Z-disk. If this protein (nexilin) is mutated, the movable muscle elements are no longer anchored firmly enough. The muscles then lose strength and the heart is weakened,” explains co-author of the study Dr. Tillman Dahme.

They found that in these patients, defective nexilin seems to be the major cause of heart disease. The findings also showed that the extent of the damage to the Z-disk appears to be directly related to the workload. This insight may possibly have an influence on clinical therapy.

“The nexilin dilated cardiomyopathy allowed us for the first time to describe a new form of heart muscle dilatation and define the mechanism causing it, namely destabilization of the Z-disk,” says Dahme.

Moreover, patients with a nexilin mutation could perhaps profit from early treatment with medicines that decrease cardiac stress. Also, this may lower the mechanical stress on the Z-disks and prevent progressive damage to the heart.

The findings of the study ‘Nexilin mutations destabilize cardiac Z-disks and lead to dilated cardiomyopathy’ have been published in the journal, Nature Medicine.