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Researchers have discovered a protein that contributes to healthy heart. The protein is the foundation of the smallest muscular unit, the sarcomere.
The research team was led by Wolfgang Rottbauer, Vice-Chairman of Medicine III at Heidelberg University Hospital (HUH).
In collaboration with researchers from the National Genome Research Network (NGFN), financed by the German Government, they proved that mutations of this protein nexilin set off a new type of heart failure.
Primary heart muscle disease with reduced cardiac pump function leading to enlargement of the heart chambers (dilated cardiomyopathy) is one of the most common causes of chronic heart failure.
6 new cases for every 100,000 people occur each year; 20% of these cases are genetic. The heart disease weakens cardiac cells and the heart no longer can pump resourcefully leading to dilation of the cardiac chambers.
Muscle activity takes place in the smallest unit of muscle fibre, the sarcomere. In the presence of a suitable incentive, actin and myosin filaments interact and contract the muscle. These movable elements are anchored in what are known as Z-disks. With every heartbeat, massive 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 scrutinised the genetic material of patients and confirmed a mutated Z-disk protein in 9 out of 1,000 participants.
They revealed 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 finding has been published in the November issue of Nature Medicine.
