title: Statins and myocardial remodelling: cell and molecular pathways.
abstract: The advent of statins has revolutionised the treatment of patients with raised plasma cholesterol and increased cardiovascular risk. However, the beneficial effects of this class of drugs are far greater than would be expected from lowering of cholesterol alone, and they appear to offer cardiovascular protection at multiple levels, primarily as a result of their pleiotropic activity. Indeed, their favourable effects on the heart seem to be mediated in part through reduced prenylation and subsequent inhibition of small GTPases, particularly those of the Rho family. Such statin-mediated effects are manifested by reduced onset of heart failure and improvements in cardiac dysfunction and remodelling in heart failure patients. Experimental studies have shown that statins mediate their effects on the two major resident cell types of the heart--cardiomyocytes and cardiac fibroblasts--and thus facilitate improvement of adverse remodelling of ischaemic or non-ischaemic aetiology. This review examines evidence for the cellular effects of statins in the heart, and discusses the underlying molecular mechanisms at the level of the cardiomyocyte (hypertrophy, cell death and contractile function) and the cardiac fibroblast (differentiation, proliferation, migration and extracellular matrix synthesis). The prospects for future therapies and ongoing clinical trials are also summarised.
authors: Division of Cardiovascular and Neuronal Remodelling, Leeds Institute of Genetics, Health and Therapeutics (LIGHT) and Multidisciplinary Cardiovascular Research Centre, University of Leeds, Clarendon Way, Leeds, UK. medkep@leeds.ac.uk
authors: Karen E
authors: KE
authors: Porter
authors: Neil A
authors: NA
authors: Turner
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000517:prevention & control; D002784:Cholesterol / Q000096:biosynthesis / Q000097:blood*; D005347:Fibroblasts / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D017202:Myocardial Ischemia / Q000188:drug therapy; D032383:Myocytes, Cardiac / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D020741:rho GTP-Binding Proteins