Cardiovascular Research Advance Access [Accepted Manuscript] published online on November 19, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn317
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Potential Novel Pharmacological Therapies for Myocardial Remodeling
1 Dept. of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
2 Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland
Address for correspondence: Prof. Dr. Helmut Drexler Klinik für Kardiologie und Angiologie Medizinische Hochschule Hannover Carl-Neuberg-Str.1 30625 Hannover, Germany Phone: +49-511-532-3841 Fax: +49-511-532-5412 E-mail: drexler.helmut{at}mh-hannover.de
Left ventricular (LV) remodeling 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 (AT1) receptor blocker therapy, and βblocker therapy, are related, at least in part, to their effects on LV remodeling and dysfunction. However, despite modern reperfusion therapy after MI and optimized treatment of patients with CHF, LV remodeling 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 remodeling.
Recent insights from experimental studies have provided new targets for interventions to prevent or reverse LV remodeling, 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 (MMP) 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 remodeling and dysfunction, since established pharmacological therapies may act, in part, via identical or similar signaling pathways. Nevertheless, pre-clinical 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 remodeling and dysfunction.
Time for primary review: 8 Days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B.-Y. Kang and J. L. Mehta Rosuvastatin Attenuates Ang II--Mediated Cardiomyocyte Hypertrophy via Inhibition of LOX-1 Journal of Cardiovascular Pharmacology and Therapeutics, December 1, 2009; 14(4): 283 - 291. [Abstract] [PDF]
|
|
|
|
 |
|
 J. Diez and G. Ertl A translational approach to myocardial remodelling Cardiovasc Res, February 15, 2009; 81(3): 409 - 411. [Full Text] [PDF]
|
|