Carnitine palmitoyltransferase-I, a new target for the treatment of heart failure: perspectives on a shift in myocardial metabolism as a therapeutic intervention.
Although the heart is capable of extracting energy from different types of substrates such as fatty acids and carbohydrates, fatty acids are the preferred fuel under physiological conditions. In view of the presence of diverse defects in myocardial metabolism in the failing heart, changes in metabolism of glucose and fatty acids are considered as viable targets for therapeutic modification in the treatment of heart failure. One of these changes involves the carnitine palmitoyltransferase (CPT) enzymes, which are required for the transfer of long chain fatty acids into the mitochondrial matrix for oxidation. Since CPT inhibitors have been shown to prevent the undesirable effects induced by mechanical overload, e.g. cardiac hypertrophy and heart failure, it was considered of interest to examine whether the inhibition of CPT enzymes represents a novel approach for the treatment of heart disease. A shift from fatty acid metabolism to glucose metabolism due to CPT-I inhibition has been reported to exert beneficial effects in both cardiac hypertrophy and heart failure. Since the inhibition of fatty acid oxidation is effective in controlling abnormalities in diabetes mellitus, CPT-I inhibitors may also prove useful in the treatment of diabetic cardiomyopathy. Accordingly, it is suggested that CPT-I may be a potential target for drug development for the therapy of heart disease in general and heart failure in particular.
Mengi
Sushma A
SA
Institute of Cardiovascular Sciences, University of Manitoba, St Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Dhalla
Naranjan S
NS
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology; D006801:Humans; D009206:Myocardium / Q000201:enzymology*
D004791:Enzyme Inhibitors; D002334:Carnitine O-Palmitoyltransferase