To understand the molecular mechanisms behind the functioning of the cardiac muscle to test targeted therapies against cardiomyopathies. Such is the goal of the study published in PNAS by the research group of the Department of Biology, coordinated by Vincenzo Lombardi. The team has, for the first time, discovered a method to record the mechanic performance of the molecular motor of the heart in intact cardiac cells. ("The size and speed of the working stroke of cardiac myosin in situ")
"The function of the heart is to pump blood through the vessels carrying oxygen and nutrition to the cells of the various organs”, explains Lombardi, professor of Physiology and coordinator of the Physiology Laboratory, where the experiments have been carried out. “This property is based on the alternating of the systole, the contraction phase where the pressure against the cardiac ventricles rises and blood is pushed in the arteries, and the diastolic filling, the relaxing phase where the pressure in the ventricles falls and blood coming back from the veins goes to the atria and hence to the ventricles”. The heart muscle's cells, just as those of the skeleton muscle that controls the movement of the limbs and breathing, have a striped shape due to the repeat of a 2 micron long unit, the sarcomere, whose filaments, made up of myosin protein – the molecular motor of the muscle – alternate with filaments composed of actin protein. The power necessary to rise the pressure during the systole and the consequent blood ejection is generated by the interaction of myosin molecular motors with an actin filament which is pulled towards the centre of the sarcomere.
“Flaws in the muscle's contraction and relaxation mechanism are responsible for cardiomyopathy and lead to contractile malfunctions and cardiac decompensation,” says Marco Linari, in charge of the experiment. “In the myosin protein, in particular, more than 250 mutations causing cardiomyopathies have been identified.”
The equipment of the Physiology Laboratory includes mechanical and optical-electronic instruments for the control of the sarcomere and have been so far successfully applied to determine the performances of the myosinic molecular motor in the skeletal muscle and its control. Researchers have applied for the first time a technique based on arrays of cardiac cells sectioned whole from the ventricle of a rat thanks to the collaboration with Ger Stienen of VU University Medical Center in Amsterdam, thus being able to record mechanical activity with the necessary precision to describe the motor working stroke of myosin.
"These successful results, concludes Linari, have important consequences in the medical field as it has been now proven that this technique makes it possible to detect, by measuring in situ the performance of the molecular motor, the different mutations on myosin that are at the base of some cardiomyopathies and therefore the effects of specific therapies can be tested.”
Pictured above: the research team. From left to right: Francesca Pinzauti, Gabriella Piazzesi, Massimo Reconditi, Marco Caremani, Marco Linari e Vincenzo Lombardi