A translational approach to myocardial remodelling

Abstract

The concept of cardiac remodelling was initially created to describe the changes in the anatomy of the left ventricle that occur following myocardial infarction.1 Today myocardial remodelling is used to qualify a variety of changes in the biophysiology of the cardiomyocyte, the volume and composition of cardiomyocyte, and non-cardiomyocyte compartments, and the geometry and architecture of the left ventricular chamber that occur in response to myocardial infarction, pressure or volume overload, cardiomyopathic states, and exposure to infectious or cardiotoxic agents.2 Myocardial remodelling results from modifications that are not necessarily adaptive to the initial insult, but pathological and potentially self-perpetuating in a progressive vicious circle. In addition, the effects of the insult on the final phenotype are modulated by several interfering factors, including senescence, obesity, diabetes, a number of cardiac and systemic humoral factors and, probably, genetics.3 Myocardial remodelling may result in alterations of cardiac energetics, deterioration of both diastolic and systolic function, and propensity for arrhythmias.2 Therefore, myocardial remodelling is a key determinant of the clinical course and outcome of a number of cardiac diseases. This Spotlight Issue is committed to a review of information provided by the intensive research performed in the past few years on mechanisms involved in the development, consequences, detection, and treatment of myocardial remodelling. An early feature of the maladapted heart is a loss of metabolic flexibility. Metabolic signals regulate fluxes through enzyme-catalyzed reactions in metabolic pathways and regulate transcriptional, translational, and post-translational signalling in the heart. The paradigm is emerging that metabolic remodelling precedes, triggers, and sustains functional and structural remodelling.4 Ingwall5 reviews in this Spotlight Issue the energetic phenotype of remodelled myocardium and discuss in depth the interrelations between a lower metabolic reserve and an impaired contractile reserve. Van Bilsen … *Corresponding author. Tel: +34 948 194700; fax: +34 948 194716. E-mail address : jadimar{at}unav.es