[Current pathophysiologic approaches to heart failure].
Heart failure is the consequence of cardiac remodeling that affects all the structural and functional aspects of the heart, from its ventricular geometry to the molecular components of myocytes and other myocardial cells. This remodeling is activated by biomechanical stress from the onset of the causal disease (sudden in cases of myocardial infarction and more progressively in cases of hypertension, for example). This biomechanical stress combines, depending on the cause, diverse degrees of diastolic stretching and systolic overload of the ventricles with systemic and tissular neurohormonal modifications. These mechanical and neurohormonal factors activate numerous intracellular signaling pathways, interconnected in a complex web, and lead to reprogramming the genome of the myocytes and other myocardial cells. Activation of some of these pathways leads to a beneficial adaptive remodeling (growth, cardiac hypertrophy of pregnancy and of athletes) or on the contrary to harmful remodeling (heart disease). The predominance of the stimulation of the harmful pathways over that of the beneficial pathways in heart disease is responsible for progression towards heart failure. Current research aims at identifying new pathways and participants in the beneficial and harmful remodeling of the myocardium in order to develop new drugs that will block ever more specifically the harmful pathways but also stimulate the beneficial ones, to prevent progression towards heart failure.
Mercadier
Jean-Jacques
JJ
Services d'explorations fonctionnelles et de cardiologie, AP-HP, Inserm U698, Groupe hospitalier Bichat - Claude Bernard, Paris (75), France. jean-jacques.mercadier@bch.aphp.fr
D009202:Cardiomyopathies / Q000503:physiopathology; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D015398:Signal Transduction / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology