Trimetazidine does not alter metabolic substrate oxidation in cardiac mitochondria of target patient population

Autor:	Jasenka Kraljević, N Karanovic, Zeljko Dujic, Jasna Marinovic, Carl J. Lavie, Damir Fabijanić, Ulrik Wisløff, Marija Cavar, Darija Bakovic, C Bulat, Marko Ljubkovic
Rok vydání:	2016
Předmět:	0301 basic medicine Pharmacology chemistry.chemical_classification medicine.medical_specialty Trimetazidine Fatty acid 030204 cardiovascular system & hematology Carbohydrate metabolism Biology Pyruvate dehydrogenase complex 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Endocrinology chemistry Internal medicine medicine Pyruvic acid Beta oxidation Palmitoylcarnitine Heart metabolism medicine.drug
Zdroj:	British Journal of Pharmacology. 173:1529-1540
ISSN:	0007-1188
DOI:	10.1111/bph.13454
Popis:	Background and Purpose Trimetazidine, known as a metabolic modulator, is an anti-anginal drug used for treatment of stable coronary artery disease (CAD). It is proposed to act via modulation of cardiac metabolism, shifting the mitochondrial substrate utilization towards carbohydrates, thus increasing the efficiency of ATP production. This mechanism was recently challenged; however, these studies used indirect approaches and animal models, which made their conclusions questionable. The goal of the current study was to assess the effect of trimetazidine on mitochondrial substrate oxidation directly in left ventricular myocardium from CAD patients. Experimental Approach Mitochondrial fatty acid (palmitoylcarnitine) and carbohydrate (pyruvate) oxidation were measured in permeabilized left ventricular fibres obtained during coronary artery bypass grafting surgery from CAD patients, which either had trimetazidine included in their therapy (TMZ group) or not (Control). Key Results There was no difference between the two groups in the oxidation of either palmitoylcarnitine or pyruvate, and in the ratio of carbohydrate to fatty acid oxidation. Activity and expression of pyruvate dehydrogenase, the key regulator of carbohydrate metabolism, were also not different. Lastly, acute in vitro exposure of myocardial tissue to different concentrations of trimetazidine did not affect myocardial oxidation of fatty acid. Conclusion and Implications Using myocardial tissue from CAD patients, we found that trimetazidine (applied chronically in vivo or acutely in vitro) had no effect on cardiac fatty acid and carbohydrate oxidation, suggesting that the clinical effects of trimetazidine are unlikely to be due to its metabolic effects, but rather to an as yet unidentified intracardiac mechanism.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::678c9bf7d099057dc4bfe9555f3398ae https://doi.org/10.1111/bph.13454 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.