Myocardial remodelling: pharmacological targets.
Despite considerable progress in therapy, the progressive augmentation of lifespan makes cardiac remodelling and its consequence, heart failure, a major cause of mortality and morbidity. Heart failure is consequently becoming a major goal in pharmacological research. New approaches include converting enzyme inhibitors, beta-blockers and anti-aldosterones and have demonstrated that cardiac remodelling is, at least partly, a reversible process. This review aims to establish a strategy for therapeutic research which is based on the recent advances on the molecular mechanisms of cardiac remodelling, and also to evaluate some of the new developments which are presently in progress, including new inotropic drugs, new receptors or signals blockers, nitric oxide donors, metalloproteinases and apoptotic inhibitors. Our view is clearly evolutionary and several of our conclusions may contradict current opinions, such as those which consider hypertrophy a detrimental process, hormones as a primary cause of cardiac remodelling or inotropic interventions as beneficial.
Swynghedauw
Bernard
B
Institut National de la Santé et de la Recherche Médicale, INSERMU127-INSERM and IFR Circulation, Hôpital Lariboisière, Paris, France. bernard.swynghedauw@inserm.lrb.ap-hop-paris.fr
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002303:Cardiac Output, Low / Q000188:drug therapy* / Q000503:physiopathology; D015870:Gene Expression; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000494:pharmacology; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000235:genetics / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D020030:Nitric Oxide Donors; D008666:Metalloendopeptidases