title: Potential novel pharmacological therapies for myocardial remodelling.
abstract: Left ventricular (LV) remodelling remains an important treatment target in patients after myocardial infarction (MI) and chronic heart failure (CHF). Accumulating evidence has supported the concept that beneficial effects of current pharmacological treatment strategies to improve the prognosis in these patients, such as angiotensin-converting enzyme (ACE) inhibition, angiotensin type 1 receptor blocker therapy, and beta-blocker therapy, are related, at least in part, to their effects on LV remodelling and dysfunction. However, despite modern reperfusion therapy after MI and optimized treatment of patients with CHF, LV remodelling is observed in a substantial proportion of patients and is associated with an adverse clinical outcome. These observations call for novel therapeutic strategies to prevent or even reverse cardiac remodelling. Recent insights from experimental studies have provided new targets for interventions to prevent or reverse LV remodelling, i.e. reduced endothelial nitric oxide (NO) synthase-derived NO availability, activation of cardiac and leukocyte-dependent oxidant stress pathways, inflammatory pathway activation, matrix-metalloproteinase activation, or stem cell transfer and delivery of novel paracrine factors. An important challenge in translating these observations from preclinical studies into clinical treatment strategies relates to the fact that clinical studies are designed on top of established pharmacological therapy, whereas most experimental studies have tested novel interventions without concomitant drug regimens such as ACE inhibitors or beta-blockers. Therefore, animal studies may overestimate the effect of potential novel treatment strategies on LV remodelling and dysfunction, since established pharmacological therapies may act, in part, via identical or similar signalling pathways. Nevertheless, preclinical studies provide essential information for identifying potential novel targets, and their potential drawbacks, and are required for developing novel clinical treatment strategies to prevent or reverse LV remodelling and dysfunction.
authors.affiliation: Deparment of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
authors.forename: Kai C
authors.initials: KC
authors.lastname: Wollert
authors.forename: Helmut
authors.initials: H
authors.lastname: Drexler
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D043925:Angiogenesis Inducing Agents; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D006152:Cyclic GMP / Q000378:metabolism; D015507:Drugs, Investigational / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D061965:Matrix Metalloproteinase Inhibitors; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D011480:Protease Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D033581:Stem Cell Transplantation; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000319:Adrenergic beta-Antagonists; D043925:Angiogenesis Inducing Agents; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002317:Cardiovascular Agents; D015507:Drugs, Investigational; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D011480:Protease Inhibitors; D009569:Nitric Oxide; D006152:Cyclic GMP