London, Nov 26 (Inditop.com) The heart has to be extremely durable and tough to pump 250 million litres of blood through the body in the course of a single lifetime. Now, researchers have discovered a protein that is the mainstay of the smallest muscular unit, the sarcomere, which contributes to a healthy heart.
The research group was headed by Wolfgang Rottbauer, vice-chairman of Medicine III at Heidelberg University Hospital (HUH).
Cooperating with researchers from the National Genome Research Network (NGFN), funded by the German government, they proved that mutations of this protein nexilin trigger a new type of heart failure.
Primary heart muscle disease with decreased cardiac pump function leading to enlargement of the heart chambers (dilated cardiomyopathy) is one of the most frequent causes of chronic heart failure.
Six new cases per 100,000 people occur each year; 20 percent of these cases are genetic. The heart disease weakens cardiac cells and the heart can no longer pump efficiently which leads to dilation of the cardiac chambers.
Muscle activity takes place in the smallest unit of muscle fibre, the sarcomere. In the presence of an appropriate stimulus, actin and myosin filaments interact and contract the muscle.
These movable elements are anchored in what are known as Z-disks. With every heartbeat, enormous forces act on the Z-disks.
“In our studies of zebrafish, we discovered a protein that is needed to stabilise the Z-disk. If this protein (nexilin) is mutated, the movable muscle elements are no longer anchored firmly enough,” says Rottbauer.
The muscles then lose strength and the heart is weakened,” explains Tillman Dahme, study co-author. Researchers examined the genetic material of affected patients and verified a mutated Z-disk protein in nine out of 1,000 participants.
They showed that in these patients, the defective nexilin was the major cause of heart disease, says an HUH release.
“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 destabilisation of the Z-disk,” says Dahme.
“Patients with a nexilin mutation might benefit from early treatment with medications that reduce cardiac stress. This could lower the mechanical stress on the Z-disks and prevent progressive damage to the heart,” said Rottbauer.
The results were published in the November issue of Nature Medicine.
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