Cardiovascular Research Advance Access first published online on November 19, 2008
This version [Corrected Proof] published online on December 15, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn317
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Potential novel pharmacological therapies for myocardial remodelling
1 Deparment of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany
2 Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland
* Corresponding author. Tel: +49 511 532 3841; fax: +49 511 532 5412. E-mail address: drexler.helmut{at}mh-hannover.de
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 β-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 β-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.
KEYWORDS Remodelling; Heart
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