The research group on http://en.vhir.org/portal1/area.asp?s=recerca&contentid=1274 Cardiocirculatory pathology of the Vall d'Hebron Research Institute (VHIR), a member group of the CIBER of Cardiovascular Diseases (CIBERCV) and led by Dr. David García-Dorado, has conducted a study in an animal model of rats in which they have described the new axis of cell signaling that leads to myocardial hypertrophy formed by Calpain and GRK2 and have shown that the inhibition of this axis by Caliphate oral inhibitors are an innovative and effective strategy to attenuate myocardial hypertrophy and remodeling induced by both acute myocardial infarction and chronic non-ischemic stress. The study, in which researchers from the Severo Ochoa Molecular Biology Center of the Autonomous University of Madrid have also participated, has been published in the journal https://link.springer.com/article/10.1007/s00395-019-0730-5 Basic Research in Cardiology.Heart hypertrophy, an increase in the size of heart cells and heart weight, is an initially effective response to the overload of cardiac muscle work, but may end up becoming a problem in itself, making it difficult the function of the heart and causing cardiac insufficiency and arrhythmias, a process called adverse ventricular remodeling. In spite of its high prevalence and its enormous health and social impact, the effectiveness of current treatments to prevent or reduce it is limited, so the identification of new targets and the development of treatments that interfere with molecular and cellular mechanisms involved in the ventricular remodeling and progressive development of cardiac insufficiency is a priority objective.In previous studies, this group of researchers had shown that the activation of enzymes, calpains, capable of attacking many cellular proteins (enzymes activated for the increase of intracellular calcium) plays an important role in the death of myocardial cells during the restoration of the blood flow after a period of myocardial ischaemia, and that its inhibition decreases the size of the infarct and post-infartial ventricular remodeling.In the present collaborative study, the CIBERCV groups led by Dr. David Garcia-Dorado at the VHIR and Dr. Federico Mayor, at the Universidad Autónoma de Madrid (Center for Molecular Biology Severo Ochoa), has used a myocardial hypertrophy model induced by chronic exposure of rats and mice at elevated levels of isoproterenol, an adrenal hormone, the chronic increase of activity induces hypertrophy, and it has been shown that this chronic stimulation also induces an activation of calpains.The researchers have studied the mechanisms by which chronic calcific activation produces hypertrophy and have found that a very important enzyme in the transmission of extracellular signals to cells through receptors, GRK2, plays an important role in these mechanisms. The activity of calpains causes an increase of GRK2 by increasing its synthesis and decreasing its degradation. The study shows that the oral administration of a calpain inhibitor reverses this process and is able to attenuate hypertrophy induced by the stimulation maintained with isoproterenol.These results describe a new cell signaling axis that leads to myocardial hypertrophy formed by calpain and GRK2, suggesting that the inhibition of this axis, in particular with calpain inhibitors, is an innovative and effective strategy to limit the hypertrophy and myocardial remodeling induced not only by acute myocardial infarction but by chronic non-ischemic stress.