Een stiff heart
Heart failure is the main cause of heart problems and in half of the cases, the heart is still squeezing sufficiently, but it is no longer filling properly with blood. With each beat, the heart fills with blood by relaxing and then immediately pushes a quantity of blood up into the aorta, the main artery of the body. If there’s less blood in the ventricle, this is called “diastolic heart failure”: the heart is too stiff to fill up properly, so not enough blood is squeezed out into the body.
Scar tissue
This is common by women, and generally by people with diabetes, overweight or both. There are other causes: muscle cells that are so damaged that they no longer move, and then become scar tissue, or fibrosis. The other cause is precipitation of certain sugar-bound proteins. The third cause is loss of elasticity of the myocardial cells themselves; they no longer stretch by themselves.
Medications can influence the timing of the heart rhythm to give it more time to fill up, but if the heart remains stiff, it is not enough.
What we are looking for, is to directly influence the mechanism by which the heart does not relax properly.
Less accumulation of connective tissue
In the lab in Amsterdam, the cause of this heart stiffness was investigated by looking at pieces of heart muscle tissue from patients. To the researchers’ great surprise, patients with a stiff heart had less accumulation of connective tissue and also no precipitation of sugar-bound proteins, as is the case by people whose hearts no longer squeeze properly; usually survivors of heart attacks. Such people have heart failure due to a weakened heart.
Protein "titin"
It seems that people whose hearts did not fill up properly, had severely damaged elasticity; this is defined by the largest protein we know, which acts like a spring at both ends of the muscle cell: the protein is called “titin”. The muscle cell has 3 ways of dealing with this “titin” and all 3 fail in people with stiff hearts.
Too much titin was already too stiff;
Phosphate has to be bound to titin but this was insufficient;
Sulfur bridges in the protein need to be released to make it flexible, but this is not possible because too many sulfur bridges are bound.
The ACS Research focuses on releasing the titin, adding phosphate and unsticking sulphur bridges: those are the 3 ways that need to be investigated to make the heart relaxed.
