New targets to treat the structural remodeling of the myocardium.
Classical therapy of heart failure is based on treatment of its pre-disposing/triggering factors and of the neurohumoral activation secondary to the deterioration of cardiac function. A new view is emerging that proposes the direct intervention on the pathological structural remodeling of the myocardium as part of heart failure therapy. In fact, in conditions of chronic injury, the cardiomyocytic and the noncardiomyocytic components of the myocardium undergo a series of structural lesions (i.e., cardiomyocyte growth and death, inflammation, alterations of collagen matrix, and microvascular rarefaction) that are governed by a complex interplay of mechanisms. Our increasing knowledge of the role of these mechanisms in remodeling enables us not only to better understand how our more successful therapies work but also to explore novel therapies for the future. In this paper, we will examine recent insights from experimental and pilot clinical studies that have provided new targets for interventions to prevent or reverse inflammation, alterations of collagen matrix, and cardiomyocyte death.
Division of Cardiovascular Sciences, Centre of Applied Medical Research, University of Navarra, Pamplona, Spain.
Arantxa
A
González
Susana
S
Ravassa
Javier
J
Beaumont
Begoña
B
López
Javier
J
Díez
D016923:Cell Death / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009203:Myocardial Infarction / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000473:pathology; D058628:Myofibroblasts / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology
D018836:Inflammation Mediators; D016328:NF-kappa B; D003094:Collagen; D020782:Matrix Metalloproteinases