As we all know, only what goes in goes out: how flexible the heart walls are is therefore also crucial for the heart’s pumping function. A working group from the Institute of Physiology II at the Medical Faculty of the University of Münster has been able to show for the first time which structural elements influence this flexibility and to what extent. The study has now been published in the renowned journal Nature Cardiovascular Research.
Basically, the heart works like any other pump: during diastole it relaxes and fills with blood, during systole it contracts and pumps the vital fluid into the body’s circulation. -The elasticity of the heart walls is important here. The amount of blood that flows into the heart during diastole is also pushed out again and supplies our circulation with oxygen, among other things," explains Prof. Wolfgang Linke, who heads the working group. Better distensibility therefore means higher volume and this in turn means more blood. This raises the question: which structures influence flexibility and to what extent?
Titin, the largest muscle protein in the human body, was previously considered to be particularly influential. Like a spring, it holds together the thick and thin fibers known as filaments, which mediate the contraction of a muscle. When the muscle stretches, for example, the spring tenses and acts on the filaments - as it does during diastole. -In a mouse model, we have successively removed the individual structural elements in isolated heart preparations that could influence stretching," says Linke. This was made possible by an enzyme scissors that Linke’s research group had developed in earlier work to cut titin filaments. -In the new study, we then also eliminated other mechanical elements of the heart muscles and also looked at the extracellular matrix. Using this exclusion procedure, it was possible to investigate - slice by slice - which element makes which contribution to stretchability.
The result: the titin springs actually have the greatest influence. However, other elements also make a decisive contribution, above all the microtubule proteins and actin filaments. In addition, the extracellular matrix is not insignificant - but it only takes effect when the heart has already filled up to a large extent, i.e. the rubber band is stretched. -Using our method, we have quantified the proportion of individual elements in the stretchability for the first time. This can be the starting point for further questions, for example: Which element should be targeted therapeutically in certain heart diseases in order to improve wall distensibility? Or: Are the relatively frequently occurring genetic changes in titin the reason why the heart walls wear out in many chronic heart diseases?