Myocardial hypertrophy and the maturation of fatty acid oxidation in the newborn human heart.
After birth dramatic decreases in cardiac malonyl CoA levels result in the rapid maturation of fatty acid oxidation. We have previously demonstrated that the decrease in malonyl CoA is due to increased activity of malonyl CoA decarboxylase (MCD), and decreased activity of acetyl CoA carboxylase (ACC), enzymes which degrade and synthesize malonyl CoA, respectively. Decreased ACC activity corresponds to an increase in the activity of 5'-AMP activated protein kinase (AMPK), which phosphorylates and inhibits ACC. These alterations are delayed by myocardial hypertrophy. As rates of fatty acid oxidation can influence the ability of the heart to withstand an ischemic insult, we examined the expression of MCD, ACC, and AMPK in the newborn human heart. Ventricular biopsies were obtained from infants undergoing cardiac surgery. Immunoblot analysis showed a positive correlation between MCD expression and age. In contrast, a negative correlation in both ACC and AMPK expression and age was observed. All ventricular samples displayed some degree of hypertrophy, however, no differences in enzyme expression were found between moderate and severe hypertrophy. This indicates that increased expression of MCD, and the decreased expression of ACC and AMPK are important regulators of the maturation of fatty acid oxidation in the newborn human heart.
Yatscoff
Michael A
MA
Department of Pediatrics, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
Jaswal
Jagdip S
JS
Grant
Meghan R
MR
Greenwood
Rachel
R
Lukat
Trish
T
Beker
Donna L
DL
Rebeyka
Ivan M
IM
Lopaschuk
Gary D
GD
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D000375:Aging / Q000502:physiology; D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006352:Heart Ventricles / Q000201:enzymology / Q000473:pathology; D006801:Humans; D006984:Hypertrophy / Q000201:enzymology / Q000473:pathology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D010084:Oxidation-Reduction; D010766:Phosphorylation
D005227:Fatty Acids; D008316:Malonyl Coenzyme A; D055372:AMP-Activated Protein Kinases; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase; D000103:Acetyl-CoA Carboxylase