title: [Molecular targets and novel pharmacological options to prevent myocardial hypertrophic remodeling].
abstract: Myocardial hypertrophic remodeling is a pathophysiological feature of several cardiac conditions and is the hallmark of hypertrophic cardiomyopathy (HCM), the most common monogenic inherited disease of the heart. In recent years, preclinical and clinical studies investigated the underlying molecular mechanisms and intracellular signaling pathways involved in pathologic cardiomyocyte hypertrophy and highlighted a number of possible molecular targets of therapy aimed at preventing its development. Early prevention of myocardial hypertrophic remodeling is particularly sought after in HCM, as current therapeutic strategies are unable to remove the primary cause of disease, i.e. the disease-causing gene mutation. Studies on transgenic animal models or human myocardial samples from patients with HCM identified intracellular calcium overload as a central mechanism driving pathological hypertrophy. In this review, we analyze recent preclinical and clinical studies on animal models and patients with HCM aimed at preventing or modifying hypertrophic myocardial remodeling. Mounting evidence shows that prevention of pathological hypertrophy is a feasible strategy in HCM and will enter the clinical practice in the near future. Considering the close mechanistic similarities between HCM and secondary hypertrophy, these studies are also relevant for the common forms of cardiac hypertrophy, such as hypertensive or valvular heart disease.
authors.affiliation: Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino (NeuroFarBa), Università degli Studi, Firenze.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Coppini
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi, Firenze - Centro di Riferimento Regionale per le Cardiomiopatie, Azienda Ospedaliero-Universitaria Careggi, Firenze.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Ferrantini
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi, Firenze.
authors.forename: Corrado
authors.initials: C
authors.lastname: Poggesi
authors.affiliation: Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino (NeuroFarBa), Università degli Studi, Firenze.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mugelli
authors.affiliation: Centro di Riferimento Regionale per le Cardiomiopatie, Azienda Ospedaliero-Universitaria Careggi, Firenze.
authors.forename: Iacopo
authors.initials: I
authors.lastname: Olivotto
mesh_terms: D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002312:Cardiomyopathy, Hypertrophic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D019317:Evidence-Based Medicine; D005240:Feasibility Studies; D020022:Genetic Predisposition to Disease; D006349:Heart Valve Diseases / Q000150:complications; D006801:Humans; D006973:Hypertension / Q000150:complications; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D012307:Risk Factors; D015398:Signal Transduction; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D002317:Cardiovascular Agents