Targeting Myocardial Metabolism for the Treatment of Stable Angina

Author(s): Dimitris Tousoulis, Constantinos Bakogiannis, Alexandros Briasoulis, Nikolaos Papageorgiou, Emmanuel Androulakis, Gerasimos Siasos, George Latsios, Anna-Maria Kampoli, Marietta Charakida, Kostas Toutouzas, Christodoulos Stefanadis

Journal Name: Current Pharmaceutical Design

Volume 19 , Issue 9 , 2013

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The goals of pharmacological treatment of stable angina pectoris are to improve quality of life by reducing the severity and/or frequency of symptoms and also the long-term prognosis. Patients with coronary artery disease have viable but dysfunctional myocardium. The metabolism of the ischemic myocardium is characterized by a shift from fatty acid to glucose as a preferred substrate and a decline in the levels of ATP. Targeting myocardial metabolism as a pharmacologic approach for chronic angina is based on the concept that metabolic adaptive mechanisms during ischemia resemble fetal energy metabolism by shifting substrate use towards glucose metabolism. Potential pharmacologic approaches should target i) the suppression of lipolysis and the plasma fatty acid levels and subsequent uptake and oxidation by the heart, ii) direct inhibition of the enzymes of fatty acid beta-oxidation, iii) inhibition of carnitine palmitoyl transferase- I (CPT-1). Currently, there are no approved medications directly targeting myocardial metabolism. However, in the last two years a number of medications indirectly targeting cardiac metabolism have been tested in small clinical trials, and some of them appear to be promising potential therapies for stable angina. This review summarizes the main aspects of myocardial metabolism and focuses on the therapeutic approaches that could offer clinical benefit in patients with stable angina.

Keywords: Myocardial metabolism, stable angina, free fatty acids, CPT inhibitors, ranolazine, prognosis, lipolysis, clinical trials, fatty acid beta-oxidation, cardiac metabolism

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Article Details

Year: 2013
Page: [1587 - 1592]
Pages: 6
DOI: 10.2174/1381612811319090006
Price: $65

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