title: Molecular determinants of myocardial hypertrophy and failure: alternative pathways for beneficial and maladaptive hypertrophy.
abstract: The implementation of molecular biological approaches has led to the discovery of single genetic variations that contribute to the development of cardiac failure. In the present review, the characteristics that are invariably associated with the development of failure in experimental animals and clinical studies are discussed, which may provide attractive biological targets in the treatment of human heart failure. Findings from the Framingham studies have provided evidence that the presence of left ventricular hypertrophy is the main risk factor for subsequent development of heart failure in man. Conventional views identify myocardial hypertrophy as a compensatory response to increased workload, prone to evoke disease. Recent findings in genetic models of myocardial hypertrophy and human studies have provided the molecular basis for a novel concept, which favours the existence of either compensatory or maladaptive forms of hypertrophy, of which only the latter leads the way to cardiac failure. Furthermore, the concept that hypertrophy compensates for augmented wall stress is probably outdated. In this article, we provide the molecular pathways that can distinguish beneficial from maladaptive hypertrophy.
authors.affiliation: Department of Cardiology, Academic Hospital Maastricht, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lips
authors.forename: Leon J
authors.initials: LJ
authors.lastname: deWindt
authors.forename: Dave J W
authors.initials: DJ
authors.lastname: van Kraaij
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
mesh_terms: D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D005260:Female; D005355:Fibrosis / Q000473:pathology; D006333:Heart Failure / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics* / Q000473:pathology; D007424:Intracellular Fluid / Q000737:chemistry; D008297:Male; D032342:Muscle Cells / Q000473:pathology; D009154:Mutation / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D002118:Calcium